Role of APOC3 3238C/G, APOB 12669G/A and SCARB1 1050C/T polymorphisms, their expression in patients of HIV-associated lipodystrophy

HariOm Singh; Shyamveer; Chandrashekhar Jori; Supriya D Mahajan; Ravikumar Aalinkeel; Kathiravan Kaliyappan; Meenakshi Bhattacharya; Mohammad Khalid Parvez; Mohammed S Al-Dosari

doi:10.1016/j.heliyon.2024.e30519

. 2024 May 1;10(9):e30519. doi: 10.1016/j.heliyon.2024.e30519

Role of APOC3 3238C/G, APOB 12669G/A and SCARB1 1050C/T polymorphisms, their expression in patients of HIV-associated lipodystrophy

HariOm Singh ^a,^⁎, Shyamveer ^a, Chandrashekhar Jori ^a, Supriya D Mahajan ^b, Ravikumar Aalinkeel ^b, Kathiravan Kaliyappan ^b, Meenakshi Bhattacharya ^c, Mohammad Khalid Parvez ^d, Mohammed S Al-Dosari ^d

PMCID: PMC11089352 PMID: 38742060

Abstract

Apolipoproteins and Scavenger Receptor Class B1 (SCARB1) proteins are involved in the etiology of HIV-associated lipodystrophy (HIVLD). APOC3 3238C/G, APOB 12669G/A and SCARB1 1050C/T polymorphisms were linked with increased level of APOB, TG, HDL-C and risk of cardiovascular diseases (CVDs). Hence, we evaluated the genetic variations of APOC3 3238C/G, APOB 12669G/A and SCARB1 1050C/T in 187 patients of HIV (64 with HIVLD, 123 without HIVLD) and 139 healthy controls using PCR-RFLP and expression by qPCR. The genotypes of SCARB1 1050 TT and APOB 12669AA showed a risk to severe HIVLD (P = 0.23, OR = 4.95; P = 0.16, OR = 2.02). The APOC3 3238 GG genotype was associated with a lesser risk of severe HIVLD (P = 0.07, OR = 0.22). The APOB 12669 GA genotype was associated with a greater risk of HIVLD severity in patients with impaired LDL, triglyceride (TG), and cholesterol levels (P = 0.34, OR = 4.13; P = 0.25, OR = 3.64; P = 0.26, OR = 5.47). Similarly, APOB 12669AA genotypes in the presence of impaired triglyceride levels displayed the susceptibility to severity of HIVLD (P = 0.77, OR = 2.91). APOB 12669 GA genotype along with impaired HDL and cholesterol levels indicated an increased risk for HIVLD acquisition among patients without HIVLD (P = 0.42, OR = 2.42; P = 0.26, OR = 2.27). In patients with and without HIVLD, APOC3 3238CG genotypes having impaired cholesterol and glucose levels had higher risk for severity and development of HIVLD (P = 0.13, OR = 2.84, P = 0.34, OR = 1.58; P = 0.71, OR = 1.86; P = 0.14, OR = 2.30). An increased expression of APOB and SCARB1 genes were observed in patients with HIVLD (+0.51 vs. −0.93; +4.78 vs. +3.29), and decreased expression of APOC3 gene was observed in patients with HIVLD (−0.35 vs. −1.65). In conclusion, the polymorphisms mentioned above were not associated with the modulation of HIVLD. However, in the presence of impaired triglyceride, HDL, cholesterol and glucose levels, APOB 12669AA and 12669 GA, APOC3 3238CG genotypes indicated a risk for the development and severity of HIVLD.

Keywords: APOC3, APOB, SCARB1, Genetic polymorphism, HIVLD

Highlights

•
APOC3 3238GG genotype was associated with a reduced risk of severe HIVLD.
•
APOC3 3238C/G, APOB 12669G/A, and SCARB11050C/T polymorphisms did not significantly differ among the groups.
•
Gene polymorphisms showed a higher risk for severity and development of HIVLD in patients having cardiac comorbidities.

1. Introduction

HIV-associated lipodystrophy (HIVLD) includes morphological and metabolic alterations in fat and glucose levels [1]. Patients who are on antiretroviral therapy, especially on protease inhibitors, were observed to be linked with lipodystrophy [2]. The abnormalities in the synthesis, processing and breakdown of lipoproteins cause dyslipidemia. Worldwide, lipoatrophy was reported to affect 13.3 %–52.9 % of people living with HIV (PLWH) [[3], [4], [5], [6]]. The prevalence of lipodystrophy in India ranges from 22 to 60.7 % [7,8]. Long-term lipodystrophy is linked to cardiovascular disease risk (CVD) [9]. In PLWH, antiretroviral therapy (ART) medication has a different impact on fat levels in different people [[10], [11], [12]]. The pathogenesis of lipodystrophy (LD) is poorly understood [13]. A host genetic predisposition has been postulated [9].

By interacting with lipoprotein receptors, apolipoproteins regulate the uptake of lipoproteins into cells and perform a role in the transport of lipids [14,15]. Apolipoproteins are linked to numerous metabolic illnesses, including diabetes, hyperlipidemia, atherosclerosis, and Alzheimer's disease [16].

Apolipoprotein C3 (APOC3) has a role in the metabolism of triglycerides [[17], [18], [19], [20], [21], [22], [23], [24], [25], [26]]. Lipoprotein lipase (LPL) and Hepatic lipase (HL) help in the absorption of particles containing high triglycerides. APOC3 inhibits LPL and HL enzymes and regulates lipid metabolism. APOC3 is found on chromosome 11 and encodes a 79 amino acids glycoprotein [27]. The APOC3 gene is reported to have two polymorphisms at its promoter regions (−455 and −482) and one at the 3′ untranslated region (UTR) 3238. Polymorphisms in APOC3 (−455T/C, −482C/T) were associated with lipoatrophy and dyslipidemia in patients on highly active antiretroviral therapy (HAART) [28]. Conversely, hypertriglyceridemia was associated with the APOC3 -3238C/G (rs5128) polymorphism [[29], [30], [31]]. Triglyceride (TG) elevation and an increased risk of cardiovascular disease have been associated with polymorphisms in the APOC3 gene [32]. The APOC3 3238G allele influences expression and, thus, regulation of the APOC3 gene [33,34]. Increased levels of plasma, TG [30,[35], [36], [37], [38]], low-density lipoprotein (LDL) cholesterol, raised blood pressure (BP), increased risk of congenital heart abnormalities (CHDs) [[39], [40], [41]] have been linked to the APOC3 3238G allele.

The transportation, metabolism, and control of cholesterol excretion are the main functions of apolipoprotein B (APOB) [42,43]. APOB binds with receptors of low-density lipoprotein (LDLRs) responsible for the uptake of LDL in a receptor-mediated manner [44]. The APOB gene is located on chromosome 2p23–24 and is 45 kb long, with 29 exons and 28 introns [45]. APOB 4154 G/A polymorphism at exon 29 results in a change from lysine to glutamine [46]. The restriction site for EcoR1 in the APOB gene is lost due to nucleotide substitution. The carrier allele 12669A of the APOB (12669G/A) affects the APOB concentration [[46], [47], [48]]. APOB rs676210 and rs1042034 polymorphisms impact coronary artery disease (CAD), hyperlipidemia and atherosclerosis risk [49]. APOB gene polymorphisms have been associated with altered HDL, VLDL, and LDL-C [48,[50], [51], [52], [53]]. Elevated APOB levels are associated with higher susceptibility to early atherosclerosis and CAD [[54], [55], [56], [57]].

The SCARB1 protein is involved in the cellular transportation of cholesterol [58,59]. SCARB1 gene is located on chromosome 12q24.31, encodes an 82 kD protein, and consists of 509 amino acids. The liver and adrenal glands are the primary sites of expression for SCARB1, which helps facilitate the selective absorption of HDL-C. SCARB1 can bind with HDL LDL [60] and VLDL [[61], [62], [63], [64], [65]]. When SR-B1 attaches to lipoproteins, it selectively absorbs cholesterol esters [[61], [62], [63]]. The polymorphism SCARB1 1050C/T (rs5888) was correlated with myocardial infarction (MI) [66] and CAD risk [67,68]. The SCARB1 rs5888 polymorphism affects the triglyceride, APOB, and HDL-C levels [66]. The SCARB1 1050 TT genotype has shown a risk for CAD [67]. Low HDL-C concentrations were linked to the SCARB1 1050 TT genotype [66], while greater TG levels were linked to the 1050CC genotype [69]. Till now, the role of APOC3 3238C/G, APOB 12669G/A, and SCARB1 1050C/T polymorphisms in the modulation of HIVLD have not been reported. Hence, we investigated the association of APOC3 3238C/G, APOB 12669G/A, and SCARB1 1050C/T polymorphisms and their expression in the modulation of HIVLD and its occurrence in healthy individuals, and their expression.

2. Materials and methods

2.1. Subjects

The study design was a multicentric cross-sectional observational study. The Government Medical College, Aurangabad, MH, was the recruitment site where we enrolled 187 participants (HIV positive) between years 2021–22. The study cases (included 64 individuals with HIVLD who had lipodystrophy, lipoatrophy, or dyslipidemia in their clinical presentation) and controls (included 123 individuals without HIVLD who had no sign of lipodystrophy, lipoatrophy, or dyslipidemia in their clinical presentation) were recruited. During routine clinic visits, trained medical professionals (i.e., physicians) at the ART+ Centre, GMC, and Hospital performed clinical assessments of lipoatrophy and lipohypertrophy. The Criteria for recruitment of study participants are shown in Table 1.

Table 1.

Criteria for recruitment of Study participants.

Subjects	Inclusion Criteria	Exclusion Criteria
HIV patients with lipodystrophy (N=64)	a)HIV-AIDS patients suffering metabolic disorder dyslipidemia, as determined by the estimation of lipid profiles after a 14-hour fast, and who had (i) triglyceride levels >150 mg/dL, (ii) HDL levels < 35 mg/dL, (iii) LDL levels >120 mg/dL, (iv) cholesterol levels >200 mg/dL (v) HIV/AIDS patients with clinical signs of lipodystrophy and lipoatrophy. b) HIV-infected patients who have been on ART for prolonged periods, for a minimum of one year.	a)Patients with HIV- infection who also have co-existing conditions like diabetes, tuberculosis, hepatitis B or C, cancer, autoimmune diseases, or cardiovascular disease history. b)Patients with HIV-1 infection who regularly drink alcohol or are drug users.
HIV patients without lipodystrophy (N=187)	a)HIV-1-infected patients were treated with ART for at least one year b) HIV-infected patients who were not related to dyslipidemia, lipoatrophy, or lipodystrophy syndrome c) Gender and age were compatible.	a) Patients with lipoatrophy or dyslipidemia b) HIV-infected patients who also have other illnesses such as cancer, diabetes mellitus, hepatitis B or C, TB, or any autoimmune disease c) Patients who regularly drank alcohol d) Patients who indulged in recreational drug use.
Healthy Controls (N=139)	a) Volunteer participation for the study b) Age and Gender match with cases c) who were free from HIV, Hepatitis B, C, and tuberculosis, age-matched, and serum-negative from the HIV-ELISA test	a) Any individual who has fever b) Any person who has evidence of HIV infection c) Any individual who has hepatitis B, C and Tuberculosis

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ICMR-National AIDS Research Institute ethics committees have approved the study. The consent from each participant were obtained.

Lipohypertrophy was defined as vascular fat gain in at least one of the following areas: the trunk (wider waist circumference), neck or back base (buffalo hump), and breasts. In contrast, lipoatrophy was defined as a subcutaneous fat loss in one or more regions such as the face (gaunt face and sunken eyes), buttocks, and limbs (skinny with prominent veins, muscles, or bones). Dyslipidemia was identified by examining the lipid profile, which includes triglycerides, LDL cholesterol, and HDL-C.

2.2. DNA and RNA extraction

Two ml blood samples were taken from recruited patients, stored at −80 °C. The QIAamp DNA Blood kit (Qiagen, Germany) and Nucleospin RNA Blood Kit (Takara Bio, Japan) were used to extract the genomic DNA and RNA from blood samples following the kit's instructions.

2.3. Genotyping

The APOC3 3238C/G, APOB 12669G/A, and SCARB1 1050C/T polymorphisms were genotyped in recruited subjects for each group using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The primers for gene amplifications APOC3 3238C/G, APOB 12669G/A, and SCARB1 1050C/T were taken [66,70,71]. In a 25 μl PCR reaction, 100–150 ng of genomic DNA was used as standards for gene amplification, along with ten pmol of FP and RP (primers), ten mM dNTPs mix, 1 U Taq DNA polymerase and 10X taq Buffer (Bangalore Genei, India).

Following PCR, reaction conditions for the APOC3 3238C/G: initial denaturation temperature 94 °C for 5 min; 35 cycles of denaturation at 94°C for 30 sec; annealing temperature 59 °C for 30 sec; extension at 72 °C for 45 sec; and a final extension at 72 °C for 10 min. For APOB 12669G/A, the following PCR reaction conditions were used: initial denaturation at 94 °C for 5 min; 35 cycles of denaturation at 94 °C for 1 min; annealing at 59 °C for 1 min; extension at 72 °C for 45 sec; and a final extension at 72 °C for 5 min. For the SCARB1 1050C/T, the following PCR reaction conditions were used: initial denaturation at 94 °C for 5 min; 35 cycles of denaturation at 94 °C for 30 s; annealing at 70 °C for 30 sec; extension at 72 °C for 45 sec; and a final extension at 72 °C for 7 min. The restriction enzymes SstI, EcoR1, and Hin1I (MBI Fermentas Inc., Glen Burnie, MD, USA) were used to digest the amplified APOC3, APOB, and SCARB1 products, respectively. Genotyping after restriction digestion of APOC3, APOB, and SCARB1 was performed on 10 % and 15 % polyacrylamide gels using molecular weight markers and visualized after staining with ethidium bromide. Based on the sequence and location of SNPs, the genotypes of APOC3 3238C/G, APOB 12669G/A, and SCARB1 1050C/T polymorphisms were assigned as follows: for APOC3: 596 bp for the CC genotype; 596 bp, 371 bp, and 225 bp for the CG genotype; and 371 bp and 225 bp for the GG genotype; for APOB: 480 bp for the AA genotype; 480 bp for the AA genotype; 480 bp, 253 bp, and 227 bp for the AG genotype; 253 bp and 227 bp for the GG genotype; and for SCARB1: 187 bp and 31 bp to the CC genotype; 218 bp, 187 bp, and 31 bp to the CT genotype; and 218 bp to the TT genotype (Table 2). A Veriti 96-well plate thermal cycler (Applied Biosystems, USA) performed all reactions. On a 2 % agarose gel, PCR products were run with molecular weight markers, and the band was visualized with EtBr staining. Twenty percent of samples were re-genotyped by other laboratory personnel to avoid differences in genotyping. Ten percent of the samples underwent sequencing to prevent the genotyping error.

Table 2.

Primer sequence and restriction enzymes are used for the genotyping of candidate genes.

Candidate Genes	Primer Sequences	PCR Product	Restriction Enzyme	RFLP (Genotypes)
APOC33238C/G (rs5128)	FP-5’-CATGGTTGCCTACAGAGG -3’ RP-5’-TGACCTTCCGCACAAAGC -3’	590 bp	SstI	CC=590bp CG=590, 365, 225bp GG=365, 225bp
APOB12669G/A (rs1042031)	FP-5’- GCTCACCCTGAGAGAAGTGTCTTCA-3’ RP-5’-CATAGTGCAAAGTTCCTCCCTAGTG -3’	376 bp	EcoRI	GG=260, 116bp GA=376, 260, 116bp AA=376bp
SCARB11050C/T (rs5888)	FP-5-CCTTGTTTCTCTCCCATCCTCACTTCCTCA ACGC-3’ RP-5’- CACCACCCCAGCCCACAGCAGC-3’	218 bp	Hin1I	CC=187, 31bp CT=218, 187, 31bp TT=218bp

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2.4. qPCR analysis

A qPCR machine was used for the selective amplification and quantitative detection of the APOB, APOC3, and SCARB1 genes. Extracted RNA was used to synthesize cDNA using the PrimeScriptTM RT Reagent Kit (Perfect Real Time) (Takara Bio; Catalogue #RR037A). SYBR green was used in real-time PCR reactions using the Applied Biosystems 7500 Fast Real-Time PCR equipment. TB Green Premix Ex TaqII (2X)-5 μl, Forward Primer (10 μM)-0.4 μl, Reverse Primer (10 μM)-0.4 μl, ROX Reference Dye or Dye II (50X)-0.2 μl, cDNA solution)-1μl and molecular-grade water were used to construct the qPCR reaction mixture, which had a total volume of 10 μl. The TB Green® Premix Ex TaqTM II (Tli RNaseH Plus) and Takara Bio (Catalogue #RR820A) kit were used to carry out the reaction. The details of the primers used in this study are provided in Table 3.

Table 3.

Primer sequences used for qPCR analysis.

Name of gene	Nucleotide sequences
APOC3	Forward Primer: 5’-AGCCTTGACCTTTCACATCTC-3’ (Sense) Reverse Primers: 5’-AAGTCAAACCCTGCCATCTC-3’ (Antisense)
APOB	Forward Primer: 5’- CCCTCAGTCCTCTCCAGATAAA-3’ (Sense), Reverse Primer: 5’-GCTGCCTCTTCTTCCCAATTA-3’ (Antisense)
SCARB1	Forward Primer: 5’-ATCCGGAGCCAAGAGAAATG-3’ (Sense) Reverse Primer: 5-ATGTCATCAGGGATTCAGAATAGG-3’ (Antisense),
GAPDH	Forward Primer: 5’-GGCTGCCATCAAGGAGGAAT-3’ (Sense) Reverse Primer: 5-GCAATTCCAGCCTTGGCATC-3’ (Antisense)

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2.5. Data analysis

The mean ± standard deviations have been displayed for the age variables. The χ2 goodness-of-fit test ascertained the Hardy-Weinberg in healthy control samples. Fisher's exact test was used to ascertain the research groups' genotype distribution. Using regression analysis, odds ratios (OR) and the 95 % confidence interval (CI) were calculated. SPSS software version 23 was utilized for analysis, and a P-value of less than 0.05 was considered statistically significant. Ct values from qPCR data were analyzed using a graph pad prism. To plot the bar diagram, a spreadsheet in Excel was utilized.

3. Results

3.1. Demographic profile

The average ages and standard deviations of HIV patients with and without lipodystrophy and healthy controls were 39.45 ± 7.46 yrs, 37.39 ± 7.48 yrs, and 38.41 ± 8.38 yrs, respectively. The characteristics of recruited participants shown in Table 4.

Table 4.

Characteristics of patients with and without HIV-associated lipodystrophy and healthy controls.

Subjects	Patients with HIVLD	Patients without HIVLD	Healthy controls
Total Number	64	123	139
Mean age and standard deviation (Years ± SD)	39.45 ± 7.46	37.39 ± 7.48	38.41 ± 8.38
Females	33(51.56%)	64(50.04%)	76(45.3%)
Males	31(48.44%)	59(47.96%)	63 (54.7%)
Ethnicity	Western India	Western India	Western India
Cholesterol status
Normal Cholesterol level (<200 mg/dL)	48(75%)	79 (64.23%)	139 (100%)
Impaired Cholesterol level (>200 mg/dL)	16(25%)	44 (77.23%)	-
Triglyceride status
Normal Triglyceride level (< 150 mg/dL)	35(54.68%)	123 (100%)	139 (100%)
Impaired Triglyceride level (> 150 mg/dL)	29(45.32%)	0 (0.0%)	-
LDL Status
Normal LDL level (<120mg/dL)	23(35.94%)	123(100%)	139 (100%)
Impaired LDL level (>120mg/dL)	41(60.06%)	0 (0.0%)	-
HDL Status
Normal HDL level (>35 mg/dL)	53(82.81%)	108 (87.80%)	139 (100%)
Impaired HDL level (<35 mg/dL)	11(17.19%)	15 (12.20%)	-
Glucose Status
Normal Glucose level (<100mg/dL)	57(89.06%)	99 (80.48%)	139 (100%)
Impaired Glucose level (>100mg/dL)	7(10.94%)	24 (19.52%	-

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3.2. Occurrence of APOC3 3238C/G, APOB 12669G/A, SCARB1 1050C/T polymorphisms in patients with and without HIVLD

The genotype and allele frequencies of APOC3 3238C/G, APOB 12669G/A, and SCARB1 1050C/T polymorphisms in study case and control groups are shown in Table 5.

Table 5.

Frequency distribution of APOC3 3238C/G, APOB 12669G/A and SCARB1 1050C/T polymorphisms in patients with and without HIV-associated lipodystrophy.

APOC3 3238C/G Polymorphism
Genotypes	Patients with HIVLD N=64	Patients without HIVLD N=123	P-Value	OR( 95%CI)
CC	35 (54.7%)	59 (48.0%)	1	Reference
CG	27 (42.2%)	49 (39.8%)	0.94	0.93(0.47-1.83)
GG	2 (3.1%)	15 (12.2%)	0.07	0.22(0.03-1.13)
Alleles	Patients with HIVLD 2N=128	Patients without HIVLD 2N=246	P-Value	OR( 95%CI)
C	97 (93%)	167 (95.0%)	1	Reference
G	31 (7%)	79 (5%)	0.14	0.68(0.40-1.13)

APOB 12669G/A Polymorphism
Genotypes	Patients with HIVLD N=64	Patients without HIVLD N=123	P-Value	OR( 95%CI)
GG	54(84.4%)	109(88.6%)	1	Reference
GA	7(10.9%)	13(10.6%)	0.93	1.09(0.37-3.14)
AA	3(4.7%)	1(0.8%)	0.23	4.95(0.35-69.82)
Alleles	Patients with HIVLD 2N=128	Patients without HIVLD 2N=246	P-Value	OR( 95%CI)
G	115(89.84%)	231(93.90%)	1	Reference
A	13(10.15%)	15(6.10%)	0.22	1.74(0.75-4.02)

SCARB1 1050C/T Polymorphism
Genotypes	Patients with HIVLD N=64	Patients without HIVLD N=123	P-Value	OR( 95%CI)
CC	17(26.6%)	45(36.6%)	1	Reference
CT	31(48.4%)	57(46.3%)	0.40	1.44(0.67-3.11)
TT	16(25.0%)	21(17.1%)	0.16	2.02(0.79-5.20)
Alleles	Patients with HIVLD 2N=128	Patients without HIVLD 2N=246	P-Value	OR( 95%CI)
C	65(60.78%)	147(59.75%)	1	Reference
T	63(49.22%)	99(40.25%)	0.12	1.44(0.91-2.26)

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N=Total number of subjects, (%) = frequency of genotypes/alleles, Odds ratios (OR) and 95% CI confidence intervals (CI) were derived from logistic regression models comparing the homozygous wild-type genotype/allele (CC genotype and C allele for APOC3 3238C/G polymorphism, GG genotype and G allele for APOB 12669G/A polymorphism, CC genotype and C allele for SCARB1 1050C/T polymorphism were taken as reference) with other genotypes.

The APOC3 3238GG genotype was less prevalent in case groups (with HIVLD) compared with those control groups (without HIVLD) (3.1 % vs. 12.2 %, P = 0.07, OR = 0.22, 95 % CI: 0.03–1.13) and showed a reduced risk for the severity of HIVLD. APOC3 3238CC and 3238CG genotypes were distributed similarly between case and control groups (54.7 % vs. 48.0 %; 42.2 % vs. 39.8 %).

The APOB 12669AA genotype and 12669A allele were prevalent in case groups compared to the control groups (4.7 % vs. 0.8 %, P = 0.23, OR = 4.95, 95 % CI: 0.35–69.82; 10.15 % vs. 6.10 %, P = 0.22, OR = 1.74, 95%CI: 0.75–4.02) and showed a risk for the severity of HIVLD. APOB 12669GG and 12669GA genotypes were distributed almost similarly in case and control groups (84.4 % vs. 88.6 %; 10.9 % vs. 10.6 %).

The SCARB1 1050TT genotype was higher in case groups as compared to the control groups (25.0 % vs. 17.1 %, P = 0.16, OR = 2.02, 95 % CI: 0.79–5.20) and indicated a risk for the severity of HIVLD. SCARB1 1050CT genotype was comparable (48.4 % vs. 46.3 %) between case and control groups.

3.3. Occurrence of APOC3 3238C/G, APOB 12669G/A, SCARB1 1050C/T polymorphisms in patients with HIVLD, and healthy individuals

The frequency of genotype and alleles for APOC3 3238C/G, APOB 12669G/A, and SCARB1 1050C/T polymorphisms in patients with HIVLD healthy individuals are shown in Table 6. The genotype distribution of APOC3 3238C/G, APOB 12669G/A, and SCARB1 1050C/T polymorphisms in healthy individuals were in the Hardy-Weinberg equilibrium (P = 0.21, 0.64, and 0.14).

Table 6.

Frequency distribution of APOC3 3238C/G, APOB 12669G/A and SCARB1 1050C/T polymorphisms in patients with HIV-associated lipodystrophy and healthy controls.

APOC3 3238C/G Polymorphism
Genotypes	Patients with HIVLD N=64	Healthy controls N=139	P-Value	OR( 95%CI)
CC	35 (54.7%)	59 (42.4%)	1	Reference
CG	27 (42.2%)	68 (48.9%)	0.25	0.67(0.35-1.29)
GG	2 (3.1%)	12 (8.7%)	0.16	0.28(0.04-1.45)
Alleles	Patients with HIVLD 2N=128	Healthy controls 2N=278	P-Value	OR( 95%CI)
C	97 (75.78%)	186 (66.90%)	1	Reference
G	31 (24.22%)	92 (33.10%)	0.09	0.65(0.39-1.07)

APOB 12669G/A Polymorphism
Genotypes	Patients with HIVLD N=64	Healthy controls N=139	P-Value	OR( 95%CI)
GG	54 (84.4%)	111 (79.85%)	1	Reference
GA	7(10.9%)	27(19.42%)	023	0.53(0.20-1.39)
AA	3(4.7%)	1(0.71%)	0.21	6.17(0.55-157.61)
Alleles	Patients with HIVLD 2N=128	Healthy controls 2N=278	P-Value	OR( 95%CI)
G	115(89.85%)	249(89.57%)	1	Reference
A	13(10.15%)	29(10.43%)	0.87	1.01(0.47-2.11)

SCARB1 1050C/T Polymorphism
Genotypes	Patients with HIVLD N=64	Healthy controls N=139	P-Value	OR( 95%CI)
CC	17(26.6%)	39(28.1%)	1	Reference
CT	31(48.4%)	77(55.4%)	0.96	0.92(0.43-1.99)
TT	16(25.0%)	23(16.5%)	0.39	1.60(0.62-4.10)
Alleles	Patients with HIVLD 2N=128	Healthy controls 2N=278	P-Value	OR( 95%CI)
C	65(50.78%)	155(55.75%)	1	Reference
T	63(49.22%)	123(44.24%)	0.40	1.22(0.79-1.90)

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The APOC3 3238 GG genotype was less prevalent in case groups as compared to controls (3.1 % vs. 8.6 %, P = 0.16, OR = 0.28, 95 % CI: 0.04–1.45) and showed a reduced risk for the severity of HIVLD. APOC3 3238CG genotype was distributed less in case groups as compared to healthy individuals (42.2 % vs. 48.9 %).

The APOB 12669AA genotype was prevalent in patients with HIVLD compared to healthy controls (4.7 % vs. 0.71 %, P = 0.21, OR = 6.17, 95 % CI: 0.55–157.61) and showed a risk for the HIVLD severity. APOB 12669 GA genotypes were represented lesser in case groups as compared to healthy individuals (10.9 % vs. 19.42 %).

The SCARB1 1050 TT genotype was higher in case groups as compared to healthy individuals (25.0 % vs. 16.5 %, P = 0.39, OR = 1.60, 95 % CI: 0.62–4.10) and indicated a risk for the severe HIVLD. SCARB1 1050CT genotype was lesser in case groups as compared to healthy individuals (48.4 % vs. 55.4 %).

3.4. Occurrence of APOC3 3238C/G, APOB 12669G/A, SCARB1 1050C/T polymorphisms in patients without HIVLD and healthy individuals

The frequency of genotype and alleles for APOC3 3238C/G, APOB 12669G/A, and SCARB1 1050C/T polymorphisms in control group and healthy individuals are shown in Table 7. APOC3 3238CC, 3238 GG (48.0 % vs. 42.4 %, 12.2 % vs. 8.6 %), APOB 12669 GG (88.6 % vs. 79.9 %), SCARB1 1050CC (36.6 % vs. 28.1 %) genotypes were found to be higher in control group when compared to healthy individuals. The occurrence of APOC3 3238CG (39.8 % vs. 48.9 %), APOB 12669 GA (10.6 % vs. 19.4 %), SCARB1 1050CT (46.3 % vs. 55.4 %) genotypes were lesser in control groups compared to healthy individuals. Distribution of APOB 12669AA (0.8 % vs. 0.7 %) SCARB1 1050TT (17.1 % vs. 16.5 %) genotypes were found nearly similar while comparing between control group and healthy individuals.

Table 7.

Frequency distribution of APOC3 3238C/G, APOB 12669G/A and SCARB1 1050C/T polymorphisms in patients without HIV-associated lipodystrophy and healthy controls.

APOC3 3238C/G Polymorphism
Genotypes	Patients without HIVLD N=123	Healthy controls N=139	P-Value	OR( 95%CI)
CC	59 (48.0%)	59 (42.4%)	1	Reference
CG	49 (39.8%)	68 (48.9%)	0.26	0.72(0.42-1.25)
GG	15 (12.2%)	12 (8.7%)	0.75	1.25(0.50-3.14)
Alleles	Patients without HIVLD 2N=246	Healthy controls 2N=278	P-Value	OR( 95%CI)
C	167 (95.0%)	186 (66.90%)	1	Reference
G	79 (5%)	92 (33.10%)	0.88	0.96(0.65-1.40)

APOB 12669G/A Polymorphism
Genotypes	Patients without HIVLD N=123	Healthy controls N=139	P-Value	OR( 95%CI)
GG	109(88.6%)	111 (79.85%)	1	Reference
GA	13(10.6%)	27(19.42%)	0.06	0.49(0.23-1.05)
AA	1(0.8%)	1(0.71%)	0.48	1.02(0.0-37.76)
Alleles	Patients without HIVLD 2N=246	Healthy controls 2N=278	P-Value	OR( 95%CI)
G	231(93.90%)	249(89.57%)	1	Reference
A	15(6.10%)	29(10.43%)	0.13	0.58(0.29-1.16)

SCARB1 1050C/T Polymorphism
Genotypes	Patients without HIVLD N=123	Healthy controls N=139	P-Value	OR( 95%CI)
CC	45(36.6%)	39(28.1%)	1	Reference
CT	57(46.3%)	77(55.4%)	0.14	0.64(0.36-1.15)
TT	21(17.1%)	23(16.5%)	0.65	0.79(0.36-1.75)
Alleles	Patients without HIVLD 2N=246	Healthy controls 2N=278	P-Value	OR( 95%CI)
C	147(59.75%)	155(55.75%)	1	Reference
T	99(40.25%)	123(44.24%)	0.16	1.36(0.94-1.98)

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3.5. Association of polymorphisms and impaired LDL levels with HIVLD

The genotype frequencies of APOC3 3238C/G, APOB 12669G/A, and SCARB1 1050C/T polymorphisms in patients with HIVLD who have impaired and normal LDL levels are shown in Table 8. In patients of HIVLD, the distribution of APOC3 3238C/G, APOB 12669G/A, and SCARB1 1050C/T polymorphisms were not much different between impaired and normal LDL levels. However, APOB 12669 GA genotype was higher in patients with impaired LDL levels than normal LDL levels and showed an increased risk for severity of HIVLD (14.6 % vs. 4.3 %, P = 0.34, OR = 4.13, 95%CI: 0.43–97.4).

Table 8.

Frequency distribution of APOC3 3238C/G, APOB 12669G/A, SCARB1 1050C/T, polymorphisms in patients with HIV-associated lipodystrophy with impaired LDL levels.

Genotypes APOC3 3238C/G	Impaired LDL level N=41	Normal LDL level N=23	P-value	OR (95% CI)
CC	22 (53.6%)	13(56.5%)	1	Reference
CG	17 (41.5%)	10 (43.5%)	0.79	1.00 (0.31-3.23)
GG	2 (4.9%)	0 (0.0%)	-	-

*Genotypes APOB* 12669G/A**	Impaired LDL level N=41	Normal LDL level N=23	P-value	OR (95% CI)
GG	32 (78.00%)	22(95.7 %)	1	Reference
GA	6(14.6%)	1(4.3%)	0.34	4.13(0.43-97.4)
AA	3 (7.3%)	0 (0.0%)	-	-

Genotypes SCARB11050C/T	Impaired LDL level N=41	Normal LDL level N=23(%)	P-value	OR (95% CI)
CC	11(26.8%)	6(26.1%)	1	Reference
CT	21(51.2%)	10 (43.5%)	0.91	1.15(0.28-4.73)
TT	9(22.0%)	7(30.4%)	0.88	0.70(0.14-3.54)

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3.6. Association of polymorphisms and impaired triglyceride levels with HIVLD

The genotype frequency of APOC3 3238C/G, APOB 12669G/A, and SCARB1 1050C/T polymorphisms in HIV patients with and without lipodystrophy, who have impaired and normal triglyceride (TG) levels are shown in Table 9. In HIV patients with lipodystrophy, the occurrence of APOC3 3238CG, APOB 12669GA and 12669AA genotypes were higher in impaired TG level groups as compared to normal TG levels (48.3 % vs. 37.1 %, P = 0.65, OR = 1.44, 95%CI: 0.46–4.46; 17.2 % vs. 5.7 %; P = 0.25, OR = 3.64, 95%CI: 0.55–30.10; 6.9 % vs. 2.9 %, P = 0.77, OR = 2.91, 95%CI: 0.19–86.76) and showed a higher risk for HIVLD severity. SCARB1 1050CT, 1050 TT genotypes were distributed less in impaired TG levels than normal TG levels (41.4 % vs 54.3 %, P = 0.15, OR = 0.34, 95%CI: 0.08–1.38; 20.7%vs 28.6 %, P = 0.22, OR = 0.33, 95%CI: 0.06–1.67) and displayed a reduced risk for HIVLD severity.

Table 9.

Frequency distribution of APOC3 3238C/G, APOB 12669G/A, SCARB1 1050C/T, polymorphisms in patients with HIV-associated lipodystrophy with triglyceride (TG) level.

Genotypes APOC3 238C/G	Impaired TG level N=29	Normal TG level N=35	P-value	OR (95% CI)
CC	15(51.7%)	20(57.2%)	1	Reference
CG	14 (48.3%)	13(37.1%)	0.65	1.44(0.46-4.46)
GG	0(0.0%)	2(5.7%)		-

*Genotypes APOB* 2669G/A**	Impaired TG level N=29(%)	Normal TG level N=35(%)	P-value	OR (95% CI)
GG	22(75.9%)	32(91.4%)	1	Reference
GA	5 (17.2%)	2 (5.7%)	0.25	3.64(0.55-30.10)
AA	2 (6.9%)	1 (2.9%)	0.77	2.91(0.19-86.76)

Genotypes SCARB11050C/T	Impaired TG level N=29	Normal TG level N=35	P-value	OR (95% CI)
CC	11(37.9%)	6(17.1%)	1	Reference
CT	12(41.4%)	19(54.3%)	0.15	0.34(0.08-1.38)
TT	6(20.7%)	10(28.6%)	0.22	0.33(0.06-1.67)

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3.7. Association of polymorphisms and impaired HDL levels with HIVLD

The frequency of genotypes APOC3 3238C/G, APOB 12669G/A, and SCARB1 1050C/T polymorphisms between impaired and normal HDL levels among case and control groups are mentioned in Table 10. In case and control patients, the occurrence of APOC3 3238C/G, APOB 12669G/A, and SCARB1 1050C/T polymorphisms were not different between impaired and normal HDL levels.

Table 10.

Frequency distribution of APOC3 3238C/G, APOB 12669G/A and SCARB1 1050C/T, polymorphisms in patients with and without HIV-associated lipodystrophy with HDL.

HIVLD				Without HIVLD
Genotypes APOC3 3238C/G	Impaired HDL level N=11	Normal HDL level N=53	P-value OR (95% CI)	Genotypes APOC3 3238C/G	Impaired HDL level N=15	Normal HDL level N=108	P-value OR (95% CI)
CC	5(45.5%)	30(56.6%)	1 (Reference)	CC	9(60.0%)	50 (46.3%)	1 (Reference)
CG	6(54.5%)	21(39.6%)	0.63, 1.71 (0.39-7.65)	CG	3(20.0%)	46 (42.6 %)	0.23, 0.36 (0.07-1.59)
GG	0(0.0%)	2(3.8%)	-	GG	3(20.0%)	12 (11.1%)	0.95,1.39 (0.25-6.97)

*Genotypes APOB* 12669G/A**	Impaired HDL level N=11	Normal HDL level N=53	P-value OR (95% CI)	Genotypes APOB 12669G/A	Impaired HDL level N=15	Normal HDL level N=108	P-value OR (95% CI)
GG	10(90.9%)	44(83.0%)	1 (Reference)	GG	12(82.0%)	97 (89.8%)	1 (Reference)
GA	1 (9.1%)	6(11.3%)	0.80, 0.73 (0.03-7.64)	GA	3 (20.0%)	10(9.3%)	0.42, 2.42 (0.45-11.68)
AA	0 (0.0%)	3(5.7%)	-	AA	0(0.0%)	1(0.9%)	-

Genotypes SCARB1 1050C/T	Impaired HDL level N=11	Normal HDL level N=53	P-value OR (95% CI)	Genotypes SCARB1 1050C/T	Impaired HDL level N=15	Normal HDL level N=108	P-value OR (95% CI)
CC	4(36.4%)	13(24.5%)	1 (Reference)	CC	6(40.0 %)	39(36.1%)	1 (Reference)
CT	5(45.4%)	26(49.1%)	0.80, 0.63 (0.12-3.42)	CT	7(46.7%)	50(46.3%)	0.88, 0.91 (0.25-3.37)
TT	2(18.2%)	14(26.4%)	0.71, 0.46 (0.05-3.81)	TT	2(13.3%)	19(17.6%)	0.97, 0.68 (0.09-4.35)

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In case group, the APOC3 3238CG genotype was observed higher in individuals with impaired HDL levels compared to those with normal HDL levels (54.5 % vs. 39.6 %, P = 0.63, OR = 1.71, 95%CI: 0.39–7.65). However, in control group, the prevalence of APOC3 3238CG genotype was lesser in impaired HDL level than normal HDL level (20.0%vs. 42.6 %, P = 0.23, OR = 0.36, 95%CI: 0.07–1.59) and displayed a reduced risk for development of HIVLD.

The occurrence of APOB 12669GA genotypes was higher in impaired HDL levels than in normal HDL levels among control groups (20.0 % vs. 9.3 %, P = 0.42, OR = 2.42, 95%CI: 0.45–11.68), and this indicated a higher risk of developing HIVLD.

In control patients, the distribution of SCARB1 1050C/T polymorphism was comparable between impaired and normal level of HDL (mentioned in Table 10). In control groups, the distribution of SCARB1 1050CT genotype (45.4 % vs 49.1 %) was comparable between impaired and normal HDL levels, while the SCARB1 1050TT genotype occurred lesser in impaired HDL levels than normal (18.2 % vs26.4 %).

3.8. Association of polymorphisms and impaired cholesterol levels with HIVLD

The frequencies of APOC3 3238C/G, APOB 12669G/A, and SCARB1 1050C/T SNPs between normal and impaired cholesterol level among case and control groups are mentioned in Table 11. In case and control groups, the occurrence of APOC3 3238CG and APOB 12669GA genotypes were found to be increased in impaired level of cholesterol groups than normal groups (62.5%vs. 35.4 %, P = 0.13, OR = 2.84, 95%CI: 0.76–10.89 and 47.7 % vs. 35.4 %, P = 0.34, OR = 1.58, 95%CI: 0.67–3.74 and 12.5%vs. 10.4 %, P = 0.26, OR = 5.47, 95%CI: 0.48–60.24 and 15.9%vs7.6 %, P = 0.26, OR = 2.27, 95%CI: 0.63–8.34) and indicated a higher chance of HIVLD onset and severity.

Table 11.

Frequency distribution of APOC3 3238C/G, APOB 12669G/A, SCARB1 1050C/T, polymorphisms in patients with and without HIV-associated lipodystrophy with cholesterol level.

HIVLD				Without HIVLD
Genotypes APOC3 3238C/G	Impaired Cholesterol level N=16	Normal Cholesterol level N=48	P-value OR (95% CI)	Genotypes APOC3 3238C/G	Impaired Cholesterol level N=44	Normal Cholesterol level N=79	P-value OR (95% CI)
CC	6(37.5%)	29(60.4%)	1 (Reference)	CC	19(43.2%)	40(50.7%)	1 (Reference)
CG	10(62.5%)	17(35.4%)	0.13,2.84 (0.76-10.8)	CG	21(47.7%)	28(35.4%)	0.34,1.58 (0.67-3.74)
GG	0 (0.0%)	2(4.2%)	-	GG	4(9.1%)	11(13.9%)	0.91,0.77 (0.18-3.11)

*Genotypes APOB* 12669G/A**	Impaired Cholesterol level N=16	Normal Cholesterol level N=48	P-value OR (95% CI)	Genotypes APOB 12669G/A	Impaired Cholesterol level N=44	Normal Cholesterol level N=79	P-value OR (95% CI)
GG	13(81.3%)	41(85.4%)	1 (Reference)	GG	37(84.1%)	72 (91.1%)	1 (Reference)
GA	2 (12.5%)	5(10.4%)	0.26, 5.47 (0.48-60.24)	GA	7(15.9%)	6(7.6%)	0.26,2.27 (0.63-8.34)
AA	1 (6.2%)	2(4.2%)	0.74, 1.58 (0.0-25.41)	AA	0(0.0%)	1(1.3%)	-

Genotypes SCARB1 1050C/T	Impaired Cholesterol level N=16	Normal Cholesterol level N=48	P-value OR (95% CI)	Genotypes SCARB1 1050C/T	Impaired Cholesterol level N=44	Normal Cholesterol level N=79	P-value OR (95% CI)
CC	5(31.3%)	12(25.0%)	1 (Reference)	CC	19(43.2%)	26(32.9%)	1 (Reference)
CT	7(48.7%)	24(50.0%)	0.86,0.70 (0.15-3.3)	CT	14(31.8%)	43(54.4%)	0.09,0.45 (0.18-1.12)
TT	4(25.0%)	12(25.0%)	0.91,0.80 (0.13-4.7)	TT	11(25.0%)	10(12.7%)	0.61,1.51 (0.47-4.85)

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3.9. Association of polymorphisms and impaired fasting glucose levels with HIVLD

The genotype frequency of APOC3 3238C/G, APOB 12669G/A, and SCARB1 1050C/T polymorphisms between impaired and normal fasting glucose levels among case and control groups are shown in Table 12.

Table 12.

Frequency distribution of APOC3 3238C/G, APOB 12669G/A, SCARB1 1050C/T, polymorphisms in patients with and without HIV-associated lipodystrophy with glucose.

HIVLD				Without HIVLD
Genotypes APOC3 3238C/G	Impaired Glucose level N=7	Normal Glucose level N=57	P-value OR (95% CI)	Genotypes APOC3 3238C/G	Impaired Glucose level N=24	Normal Glucose level N=99	P-value OR (95% CI)
CC	3 (42.9%)	32(56.1%)	1 (Reference)	CC	8(33.3%)	51(51.5%)	1 (Reference)
CG	4(57.1%)	23(40.4%)	0.71,1.86 (0.31-11.82)	CG	13(54.2%)	36(36.4%)	0.14,2.30 (0.79-6.86)
GG	0 (0.0%)	2(3.5%)	-	GG	3(12.5%)	12 (12.1%)	0.82,1.59 (0.28-8.20)

*Genotypes APOB* 12669G/A**	Impaired Glucose level N=7	Normal Glucose level N=57	P-value OR (95% CI)	Genotypes APOB 12669G/A	Impaired Glucose level N=24	Normal Glucose level N=99	P-value OR (95% CI)
GG	6(85.7%)	48 (84.2%)	1 (Reference)	GG	24(100.0%)	85(85.9%)	1 (Reference)
GA	1 (14.3 %)	6(10.5%)	0.70,1.33 (CI LI.)	GA	0 (0.0%)	13(13.1%)	-
AA	0 (0.0%)	3(5.3%)	-	AA	0(0.0%)	1(1.0%)	-

Genotypes SCARB1 1050C/T	Impaired Glucose level N=7	Normal Glucose level N=57	P-value OR (95% CI)	Genotypes SCARB1 1050C/T	Impaired Glucose level N=24	Normal Glucose level N=99	P-value OR (95% CI)
CC	3(42.9%)	14(24.6%)	1 (Reference)	CC	6(25.0%)	39(39.4%)	1 (Reference)
CT	3(42.9%)	28(49.1%)	0.73,0.50 (0.07-3.68)	CT	14(58.3%)	43(43.4%)	0.24,2.12 (0.67-6.91)
TT	1(14.2%)	15(26.3%)	0.63,0.31 (0.01-4.14)	TT	4(16.7%)	17(17.2%)	0.81,1.53 (0.31-7.31)

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The APOC3 3238CG genotype was found to be higher in impaired glucose levels than in normal glucose levels among case and control groups (57.1 % vs. 40.4 %, P = 0.71, OR = 1.86, 95%CI: 0.31–11.82; 54.2 % vs. 36.4 %, P = 0.14, OR = 2.30, 95%CI: 0.79–6.86) and indicated a risk for severity and acquisition of HIVLD (see Table 12). In control groups, SCARB1 1050CT genotype was found to be higher in the impaired glucose level compared with normal level (54.2 % vs. 36.4 %, P = 0.14, OR = 2.30, 95%CI: 0.79–6.86) as it showed a risk for development of HIVLD.

3.10. Gene expression of APOB, APOC, and SCARB1

The expression of the APOB, APOC, and SCARB1 genes in HIV patients with and without lipodystrophy taking PIs are shown in Fig. 1. The expression of each gene was normalized during expression analysis using the housekeeping gene GAPDH expression. The APOB gene was upregulated in patients with HIVLD as compared to those without HIVLD (+0.51 vs. −0.93; 1.43-fold). APOC3 genes was down-regulated by a 1.3-fold change in LDHIV taking PIs compared to without LDHIV taking PIs (−0.35 vs. −1.65; 1.3), respectively. SCARB1 was expressed in case groups as compared to control groups (+4.78 vs. +3.29; 1.49-fold).

4. Discussion

This is the first study investigating the role of APOC3 3238C/G, APOB 12669G/A, and SCARB1 1050C/T polymorphisms in the pathogenesis of HIVLD. Despite identical exposure to ART, the occurrence of lipodystrophy in HIV-infected individuals due to Protease inhibitors (PIs) is immensely varied among HIV-infected individuals. Host genetic factors may be linked with the variation in the occurrence of HIVLD. Apolipoproteins have a role in cholesterol homeostasis and are characterized by polymorphic sites. The SR-BI is heavily involved in cholesterol metabolism. SNPs in apolipoprotein and adipocyte metabolizing genes may explain why HIVLD occurs in some individuals on PIs but not all individuals exposed to PIs. Apolipoproteins (APOC3 and APOB) and Scavenger Receptor Class B (SCARB1) gene polymorphisms influence plasma TG and LDL concentrations.

The occurrence of APOC3 3238C/G polymorphism in our healthy individuals was comparable to studies of Yin et al. (2011) and Ruixing et al. (2010) [86, 87]. In our study, the APOC3 3238C/G polymorphism was not associated with susceptibility to the development and severity of HIVLD. However, the APOC3 3238GG genotype showed a reduced risk for severity of HIVLD when compared between case and control groups (P = 0.07, OR = 0.22; P = 0.16, OR = 0.28). Similarly, our study revealed a decreased expression of the APOC3 gene in patients without HIVLD. The decreased risk of acquiring HIV-1 infection was linked to the APOC3 3238C/G polymorphism [9]. However, no correlation was found between the metabolic syndrome and the APOC3 3238C/G polymorphism [72]. The APOC3 3238G allele could not explain the association with myocardial infarction (MI) [40]. The minor allele 3238G is associated with higher plasma triacylglycerol and hypertriglyceridemia [38]. The APOC3 3238C/G polymorphism was associated with CAD and CHD due to its rare allele 3238G [38,39,41,73,74].

In our healthy individuals, the frequency of the APOB 12669G/A polymorphism was differed with studies carried out by Ahmadi et al. (2016) and Rudzińska et al. (2015). In this study, the APOB 12669AA genotype showed a higher risk for the development and severity of HIVLD (P = 0.21, OR = 6.17; P = 0.23, OR = 4.95). Similarly, our study showed an increased expression of the APOB gene. The APOB 12669G/A polymorphism did not differ significantly between pre- and postmenopausal women [71]. The prevalence of the R-allele was higher in CAD patients than in normal individuals in some subjects, but not in all populations [47,48,[75], [76], [77], [78]]. The R (mutant) allele was associated with higher risk of CAD [79,80].

The frequency of the SCARB1 1050C/T polymorphism in our healthy individuals differed to the study conducted by ArulJoth et al. (2017) [81]. In our study, the SCARB1 1050 TT genotype showed a higher risk for severity of HIVLD when compared between case and control groups (P = 0.16, OR = 2.02). Similarly, our study showed increased expression of the SCARB1 gene in case group. The minor allele 1050T of SCARB1 1050C/T polymorphism was associated with increased serum lipid levels. Increased level of serum lipid was linked with higher risk of CAD [66]. The SCARB1 rs5888 polymorphism was associated with a higher risk of CAD in the Chinese population [66] and was susceptible to developing myocardial infarction (MI) in the Indian Tamil population [65,81]. The SCARB1 1050 TT genotype has been reported as susceptible to severe CAD in the Chinese population [67]. The SCARB1 1050C/T polymorphism was associated with susceptibility to CHD [82].

In our study, patients of HIVLD having APOB 12669 GA genotype in the presence of impaired LDL level revealed a greater risk of HIVLD severity (P = 0.34, OR = 4.13). However, the small sample size could not reach at significant risk. The 3238G allele of the APOC3 3238C/G polymorphism was linked to the increased LDL levels and associated with increased risk of CHD [38,39,41,74]. APOB gene polymorphisms have been correlated with TC, LDL, HDL, and VLDL cholesterol levels [48,[50], [51], [52], [53]].

In our study, patients without HIVLD having APOB 12669 GA genotype in the presence of impaired HDL level revealed a higher risk for the development of HIVLD (P = 0.42, OR = 2.42). The risk could not be statistically significant because of the smaller sample size. APOB gene polymorphisms correlate with HDL-C levels [[48], [49], [50], [51], [52], [53]].

Similarly, patients of HIVLD having APOB 12669AA and 12669GA genotypes in the presence of impaired triglyceride level showed a trend of risk for severity of HIVLD (P = 0.77, OR = 2.91; P = 0.25, OR = 3.64). Again, the risk could not be statistically significant due to the smaller sample size.

Likewise, in the present study, patients with HIVLD having APOC3 3238CG and APOB 12669 GA genotypes in the presence of impaired cholesterol levels indicated higher risk for severity of HIVLD (P = 0.13, OR = 2.84; P = 0.26, OR = 5.47). Similarly, patients without HIVLD having APOB 12669 GA genotypes in the presence of impaired cholesterol level displayed a risk for the development of HIVLD (P = 0.26, OR = 2.27), and the risk could not be statistically significant. A study suggested a positive correlation between the APOB 12669 R-allele and elevated serum lipid levels [75].

We also analyzed the association of aforesaid polymorphisms in the presence of impaired fasting glucose levels. In case and control group, The APOC3 3238CG genotype in the presence of impaired glucose level showed a risk for severity and development of HIVLD (P = 0.71, OR = 1.86; P = 0.14, OR = 2.30). However, because of the small sample size, the risk did not reach statistical significance.

5. Conclusions

APOC3 3238C/G, APOB 12669G/A, and SCARB1 1050 C/T polymorphisms were not significantly associated with the modulation of HIVLD in the present investigation. APOB 12669 GA and APOB 12669AA genotypes in the presence of impaired LDL, triglyceride and cholesterol, and APOC3 3238CG genotype in the presence of cholesterol and glucose levels showed a higher risk for severity and development of HIVLD. The present study warrants that further studies should be carried out with a larger sample size in the same and other populations for a better understanding of the pathogenesis of HIVLD.

Ethical statement

ICMR-National AIDS Research Institute ethics committees have approved the study. The consent from each participant were obtained.

Ethical approval statement

NARI/EC/Approval/20–21/396, dated August 19, 2020.

Funding

The study was supported by a grant from the Indian Council of Medical Research (ICMR), India. The grant number is HIV/50/206/09/2020/-ECD-II.

Data availability statement

Data will available on request of corresponding Author.

CRediT authorship contribution statement

HariOm Singh: Supervision, Conceptualization. Shyamveer: Data curation. Chandrashekhar Jori: Data curation. Supriya D. Mahajan: Funding acquisition. Ravikumar Aalinkeel: Investigation. Kathiravan Kaliyappan: Data curation. Meenakshi Bhattacharya: Investigation. Mohammad Khalid Parvez: Writing – review & editing. Mohammed S. Al-Dosari: Writing – review & editing.

Declaration of competing interest

There are no conflict of interest among the Authors.

Acknowledgement

We gratefully acknowledge clinic staff Asefa Begum Khan, Shradha, and Sharad of ART Plus Centre, GMC, Aurangabad, for counselling subject participants and collecting blood samples. We are also grateful to Sachin Dhaigude, ICMR-NARI, Pune, for the collection of blood samples. The authors thank the Researchers Supporting Project Number (RSP2024R379), King Saud University, Riyadh, Saudi Arabia for supporting this study. We also extend our gratitude to Dr. Stanley A. Schwartz to facilitate the work on real-time PCR and analysis of real-time data.

Footnotes

^{Appendix A}

Supplementary data to this article can be found online at https://doi.org/10.1016/j.heliyon.2024.e30519.

Appendix A. Supplementary data

The following is the Supplementary data to this article:

Multimedia component 1

mmc1.docx^{(216.3KB, docx)}

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PERMALINK

Role of APOC3 3238C/G, APOB 12669G/A and SCARB1 1050C/T polymorphisms, their expression in patients of HIV-associated lipodystrophy

HariOm Singh

Shyamveer

Chandrashekhar Jori

Supriya D Mahajan

Ravikumar Aalinkeel

Kathiravan Kaliyappan

Meenakshi Bhattacharya

Mohammad Khalid Parvez

Mohammed S Al-Dosari

Abstract

Highlights

1. Introduction

2. Materials and methods

2.1. Subjects

Table 1.

2.2. DNA and RNA extraction

2.3. Genotyping

Table 2.

2.4. qPCR analysis

Table 3.

2.5. Data analysis

3. Results

3.1. Demographic profile

Table 4.

3.2. Occurrence of APOC3 3238C/G, APOB 12669G/A, SCARB1 1050C/T polymorphisms in patients with and without HIVLD

Table 5.

3.3. Occurrence of APOC3 3238C/G, APOB 12669G/A, SCARB1 1050C/T polymorphisms in patients with HIVLD, and healthy individuals

Table 6.

3.4. Occurrence of APOC3 3238C/G, APOB 12669G/A, SCARB1 1050C/T polymorphisms in patients without HIVLD and healthy individuals

Table 7.

3.5. Association of polymorphisms and impaired LDL levels with HIVLD

Table 8.

3.6. Association of polymorphisms and impaired triglyceride levels with HIVLD

Table 9.

3.7. Association of polymorphisms and impaired HDL levels with HIVLD

Table 10.

3.8. Association of polymorphisms and impaired cholesterol levels with HIVLD

Table 11.

3.9. Association of polymorphisms and impaired fasting glucose levels with HIVLD

Table 12.

3.10. Gene expression of APOB, APOC, and SCARB1

Fig. 1.

4. Discussion

5. Conclusions

Ethical statement

Ethical approval statement

Funding

Data availability statement

CRediT authorship contribution statement

Declaration of competing interest

Acknowledgement

Footnotes

Appendix A. Supplementary data

References

Associated Data

Supplementary Materials

Data Availability Statement

ACTIONS

PERMALINK

RESOURCES

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