Table 1.
Details of the included studies. (NS = non specified).
| Study Design (Level of Evidence) | Study Population | Age (Mean/Range) Gender |
Ethnicity | Spine Deformity | Initial Cobb Angles (Mean/Max) |
Follow-Up Period | Curve Progression Definition | Biologic Sample | Technique | Gene/s Involved Polymorphism |
Results | Authors |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Retrospective case series (IV) | 304 girls with AIS (main curve < 10°) | 12.5 ± 1.6 years 100% female |
Japanese | 189 double curves 62 right thoracic curve, 25 thoracolumbar curves 13 lumbar curves 15 triple curves |
24.6 ± 10.0° 31.3 ± 12.6° |
>1 year until growth maturation when height no longer changes | progression of 5° from initial evaluation | DNA from peripheral blood lymphocytes | PCR-RFLPs | ER gene Polymorphic first intron PvuII site and the XbaI site |
XbaJ polymorphism in the ER gene associated with curve progression (p = 0.03). |
M. Inoue (2002) |
| Retrospective case series (IV) | 304 girls with AIS (main curve < 10°) | 12.5 ± 1.6 years 100% female |
Japanese | 189 double curves 62 right thoracic curve, 25 thoracolumbar curves 13 lumbar curves 15 triple curves |
24.6 ± 10.0° 31.3 ± 12.6° |
>1 year until growth maturation when height no longer changes | progression of 5° from initial evaluation | DNA from peripheral blood lymphocytes | PCR-RFLPs | MED4 ESR1 CYP17A1 |
The XbaJ polymorphism in the ER gene was associated with curve progression (p = 0.03). |
M. Inoue
(2002) |
| Retrospective case series (IV) | 340 AIS female patients | 12–16 100% female |
Chinese | NS | ≥20° | Until skeletal maturity, 16 years, or surgical intervention | NS | Peripheral blood sample | PCR-RFLD | IGF-I Rs5742612 and rs2288377 |
Cobb’s angle higher in patients with TT genotype p = 0.04) |
Y. Yeung
(2006) |
| Retrospective Case-control study (III) |
540 AIS patients 260 healthy controls (A subgroup of 364 AIS patients had been followed up to skeletal maturity at age 16) |
AIS patients: 13.4 ± 1.4 Female: 540 (100%) Healthy controls: 13.3 ± 1.3 Female: 260 (100%) |
Chinese | -King III (24.9%) -thoracolumbar (22.6%). -King I 14.5% -King II 16.2% -King V (6.8%) -lumbar curve (8.3%) -triple curve (6.6%). |
28.9° ± 11.5° | Until skeletal maturity at age 16 | Curve progression was defined as increase in Cobb angle with greater than 5° from the initial evaluation. |
Peripheral blood sample | PCR-RFLD | ER gene Two common SNPs (PvuII and XbaI) in the intron 1 of ESR1 |
No association between curve severity and curve progression and the two SNPS (Pvull and XbaI) |
N. Tang
(2006) |
| Retrospective Case-Control Study (III) | 419 AIS patients 750 healthy controls |
AIS patients: 16.1 ± 0.93, (12–19), 89.8% female Healthy controls: 15.8 ± 0.10, (8–24), 88.3% female |
Chinese | NS | High-risk genotype: 32.11° ± 11.67° Intermediate-risk genotype: 32.25° ± 12.42° High-risk genotype: 37.91° ± 17.1° |
more than 12 months until the age of growth maturation (16 years old) |
NS | Peripheral blood leukocytes | PCR-RFLD | MATN1 gene (matrilin 1 gene): rs1188402, rs1065755 rs1149045, rs1149046, rs3828051, rs1149048, rs12404006 |
Genotype GG of Rs1149048 SNPs was statistically significant with the mean maximal Cobb angle. |
Z. Chen
(2009) |
| Retrospective cohort study (III) | 67 AIS patients with double curve 100 healthy controls |
AIS patients: 15.09 ± 2.37, 10–20 7.8% male 82.2% female Healthy controls: 15.55 ± 2.21, 10–19 25% male 75% female |
Chinese | 40 thoracic curves 12 thoracolumbar curves 15 lumbar curves |
The Cobb angle of the major curve of AIS ranged from 30° to 90°. There were 60 patients with Cobb angle >40°. |
NS | Cobb angle >30 | Peripheral blood sample | PCR | ER1 CALM1 ER1 gene: rs2234693, allele T; CALM 1 gene: rs12885713, allele T |
Significant association between double curve and CALM1 ER1 SNPs, and between Cobb angle and SNPs of ER1 gene (0.0128) |
D. Zhao
(2009) |
| Retrospective Cohort study (III) | Screening group (277): -Severe: 8 (3%) -Moderate: 34 (12%) -Mild: 235 (85%) Spine surgery practice group (257): -Severe: 28 (11%) -Moderate: 54 (21%) -Mild: 175 (68%) Male group (163): -Severe: 18 (11%) -Moderate: 18 (11%) -Mild: 127 (78%) |
9–13 at diagnosis Screening group: Female: 277 (100%) Spine surgery group: Female: 257 (100%) |
Caucasian | NS | >10° | Until skeletal maturity or sever curve | -Progression to a severe curve: Cobb angle >40° in an individual still growing. Cobb angle >50° in an individual not growing -Progression to a moderate curve: Cobb angle of 25° or greater but not reaching the severe range by skeletal maturity |
Saliva samples | Quantitative PCR | 53 SNPs identified with a previous GWAS The authors stated a prognostic test algorithm (AIS-PT, Scoliscore) with a scale (1–200) based on 53 SNP markers, cut point 40: 1–40 (≤1% risk of progression) |
Low-risk scores (<41) had NPV of 100%, 99%, and 97%, respectively, in the tested populations. (95% CI: 98.6–100.0). |
K. Ward
(2010) |
| Retrospective case series (IV) | 312 AIS patients: -90 failures of the brace treatment -222 successes of the brace treatment |
12.7 ± 1.5, (10–15) Female: 41 (87%) Male: 41 (13%) |
Chinese | Single thoracic curve 128 (32.1%) Single thoracolumbar or lumbar curve 66 (30.3%) Double major curve 118 (24.5%) |
<30: 195 patients ≥30: 117 |
14.4 ± 4.8 months, (7.2 ± 26.4) | Curve progression of more than 5° compared to the initial Cobb angle Surgical intervention because of curve progression. |
Peripheral blood sample | PCR-FLP | Single nucleotide polymorphism (SNP) sites in the genes for estrogen receptor a (rs9340799), estrogen receptor b (rs1256120), tryptophan hydroxylase 1 (rs10488682) melatonin receptor 1B (rs4753426), and matrillin-1 (rs1149048), |
Statistically significant differences between the two groups in SNP rs9340799 in ERa. |
L. Xu
(2011) |
| Retrospective Case-control study (III) | 362 AIS patients 377 age-matched controls 120 skeletally immature AIS patients who received continuous brace treatment for minimum of 2 years |
AIS patients: 15.30 ± 2.49 10–20 91.9% female Controls: 15.86 ± 0.93 14–18 90.2% female |
Chinese | Thoracic and thoracolumbar curves | 25°–40° | 30 ± 4.2 months | Curve progression of more than 5° compared to the initial Cobb angle | Peripheral blood sample | PCR-RFLP | NTF3 gene: rs1805149 SNP rs11063714 SNP |
rs11063714 SNP significantly associated with lower mean maximum Cobb angle and brace treatment success |
Y. Qiu
(2012) |
| Retrospective case-control study (III) | 529 AIS case 512 healthy controls |
AIS case: 14.54 ± 1.62 (1–18) Female: 529 (100%) Healthy controls: 14.36 ± 1.93 (11–18) Female: 512 (100%) |
Chinese | Thoracic curve | AIS case: Mean Maximum Cobb: 38.30° ± 16.71°, (20°–100°) |
NS | NS | Peripheral blood sample | PCR-RFLP | IL-17RC gene Rs708567 |
GG genotype of Rs708567 showed significant association with higher Cobb angle |
S. Zhou
(2012) |
| Retrospective Case-Control study (III) | 53 cases of AIS 54 controls |
AIS group: 14.9 ± 3.4 9–19 Females: 46 (86.8%) Males: 7 (13.2%) Control group: 29.8 ± 5.5 18–40 Females: 51 (94.4%) Males: 3 (5.6%) |
Turkish | NS | 29.88° ± 11.78° | NS | NS | Peripheral blood samples | RT-PCR |
MCM6: 6p21; 13910; 4988235 MATN1: 1p35; 1149048 VDR BsmI: 12q13.1; 1544410 |
There was no statistical difference (p < 0.05) between case and control in terms of progression of the curve |
H. Yilmaz
(2012) |
| Retrospective case-control study (III) | 300 AIS patients 300 Healthy controls |
AIS group: -12.8 ± 2.1 Female 156 (52%) Male: 144 (48%) Controls: 13.3 ± 2.8 Female: 160 (53.3%) Male: 140 (46.7%) |
Russian | Thoracic: 167 (56.1%) Thoraco-lumbar: 117 (39.2%) Lumbar: 14 (4.7%) |
10°–19°: 154 (51.3%) 20°–29°: 116 (38.7%) 30–39°: 20 (6.7%) <39°: 10 (3.3%) |
36 months | NS | Peripheral blood sample | RT-PCR |
TGF! Rs1800469 Rs1800471 |
TGFB1 gene is associated with curve severity and progression in AIS. | I. Ryzhkov (2013) |
| Retrospective Case-control study (III) | 949 AIS patients 976 age-matched normal control subjects |
AIS group: 820 girls and 129 boys Control group: 662 females and 314 males |
Chinese | NS | >20° | NS | NS | Peripheral blood sample | PCR-RFLP | LBX1 (ladybird homeobox 1) gene on chromosome 10q24.31. SNP rs11190870 near LBX1 |
TT genotype of rs11190870 Significantly associated with larger Cobb angle |
H. Jiang
(2013) |
| Retrospective Case-Control study (III) | 68 AIS patients: -33 lower-risk group: Cobb’s angle 10–40 -35 high-risk group: Cobb’s angle >40° 35 age-/sex-matched controls |
AIS group: -low-risk: 14.5 26 (80.6%) females 7 (19.4%) males -high risk: 14.9 9 (25%) males 26 (75%) females Control group: 13.4 9 (25%) males 26 (75%) females |
Korean | NS | Low risk: 25.8° High risk: 58.8° |
NS | NS | Peripheral blood samples | PCR-RFLP | CHL1 (rs10510181) DSCAM (rs2222973) LAPTM4B (rs2449539) FOXB1 (rs1437480) CBLN4 (rs448013) RRAGC (rs10493083) BRIP1 (rs16945692) MATN1 (rs1149048) MTNR1B (rs4753426) IGF1 (rs5742612) |
LAPTM4B rs2449539 significantly associated with higher risk of progression. |
E. Moon
(2013) |
| Retrospective Comparative study (II) |
2217 AIS patient -progression group (880 patients) -non-progression group (492) |
Progression group: 17.2 Female: 830 (94.3%) Male: 50 (5.7%) Non-progression group: 16.8 Female: 469 (95.3%) Male: 23 (4.7%) |
Japanese | Thoracic curve: 819 (93%) Non-Thoracic curve: 61 (7%) |
>10° | NS | >40° progression group <30° and skeletal maturation Non-progression group |
Peripheral blood sample | PCR | neurotrophin 3 (rs1063714) G protein-coupled estrogen receptor (rs3808351, rs10269151 rs4266553) tissue inhibitor of metalloproteinase (rs8179090) |
No statistical difference was found between the 4 SNPs and AIS curve progression |
Y. Ogura
(2013) |
| Retrospective cohort study (III) | 405 European AIS patients: -rare variants: 26 -No rare variants: 379 370 Chinese Han AIS patients: -rare variants: 28 -No rare variants: 342 47 Other ancestries AIS patients |
European AIS -No rare variants: Female: 326 (86%) Male: 53 -Rare variants: Female: 22 (83%) Male: 3 (17%) |
European and Chinese | Right thoracic and thoracolumbar curves | >10° | NS | NS | Peripheral blood sample | Exome sequencing | Rare damaging variants of FNB1 and FNB2 | FBN1 or FBN2 variant was associated with curve magnitude |
J. Buchan
(2014) |
| Retrospective Case-control study (III) | 248 AIS patients: -Non-progressive IS: 90 -Slowly progressive IS: 90 -rapidly progressive IS (RP-IS): 62 243 healthy female controls |
NS | Polish | Thoracic curve: 191 (77%) Lumbar curve: 51 (20.5%) Single curve: 97 (39%) Double curve: 145 (58.5%) |
NS | 3 years | The change of Cobb angle value on 2 consecutive radiographs taken at 6 months of distance | Peripheral blood samples | PCR-RFLP | ESR2 gene: Promoters: Alw NI (rs1256120) AluI (rs4986938) Rsa I (rs1256049) |
There was a difference of genotype distribution of rs4986938 between progression and non-progression groups. |
T. Kotwicki
(2014) |
| Retrospective cohort study (II) | 126 AIS patients -Progression group: 27 (21%) patients -Non-progression group: 99 (79%) |
12.2 ± 1.2 (9–15.8) 113 female (89.7%) 31 males (10.3%) |
Caucasian | NS | 10°–25° | 28.5 ± 9.9 months | Patients who had curve progression to >40 or had undergone a spinal fusion |
Saliva sample | Quantitative PCR | Prognostic test algorithm (AIS-PT, Scoliscore) with a scale (1–200). Cut point: Low risk (1 to 50 points), intermediate risk (51 to 179 points), or high risk (180 to 200 points). | No significant association between the continuous ScoliScore value and curve progression (p = 0.720). |
B. Roye
(2015) |
| Retrospective cohort study (III) | 148 patients with severe AIS: -302 patients with non-severe AIS -901 healthy controls |
Severe AIS: 15 ± 2 years (10–25) Females: 129 (87.2%) Males: 19 (12.8%) Non-severe AIS 16 ± 1 years (14–22) Females: 259 (85.7%) Males: 43 (14.3%) |
French-Canadian | NS | 56° ± 12° (37°–90°) |
NS | NS | Peripheral blood sample | Quantitative PCR | The authors stated a prognostic test algorithm (AIS-PT, Scoliscore) with a scale (1–200) based on 53 SNP markers. |
None of the SNPs used were associated. |
Q. Tang
(2015) |
| Retrospective case series (IV) | 16 AIS patients | 12.5 (10–15) |
Caucasian | NS | 25.2° (20°–33°) |
2.3 years (1–4 At least 1 year after brace treatment or skeletal maturity) |
Cobb >45° | Saliva sample | Quantitative PCR | Prognostic test algorithm (AIS-PT, Scoliscore) with a scale (1–200). Cut point:160; 160–200 (high risk of curve progression with Cobb >45°) vs. <160 (low risk of curve progression with Cobb >45°) | The mean ScoliScore among those who progressed to more than 45 degrees was higher than that among those who did not (176 vs. 112, p = 0.030). |
D. Bohl
(2016) |
| Case-only study (IV) | 670 AIS patients -313 in non-progression group -357 in progression group |
-Non-progression group: 12.3 ± 2.5 -Progression group: 12.5 ± 2.7 years |
Chinese | NS | -22.6° ± 3.7° for non-progression group -53.4° ± 12.7° for progression group. |
NS | -Cobb angle <25° at final follow-up: non-progression group. -Cobb angle >40°: progression group. |
Peripheral blood sample | Quantitative PCR | The authors stated a prognostic test algorithm (AIS-PT; Scoliscore) with a scale ranging from 1 to 200 | Allele A of rs9945359 was significantly higher in the progression group than in the non-progression group (p = 0.01). |
L. Xu
(2016) |
| Genome-wide association study (GWAS) (II) |
2142 patients with AIS 1105 in progression group 832 in non-progression group 205 patients excluded |
NS | Japanese | NS | NS | NS | Progression group: Cobb angle 40° Non-progression: Cobb Angle 30° in skeletally mature patients |
Peripheral blood sample | NS | MIR4300 microRNA host gene (SNP rs1828853) |
rs1828853 showed association with progression of AIS. |
Y. Ogura
(2017) |
| Retrospective Case-control study (III) | 2645 AIS patients 2746 healthy controls (And further replicated in 693 patients and 254 controls.) |
12.5 ± 2.1 years for the patients 16.9 ± 2.8 years for the controls |
Chinese | NS | 56.2 ± 14.3° | NS | NS | Peripheral blood sample and bilateral intraoperative facet joint tissue | SNP Genotyping Assay | BNC2 (rs10738445) |
Genotype CC h larger Cobb angle |
L. Xu
(2017) |
| Case only study (IV) | 1860 Patients with AIS -594 mild curve -326 moderate curve -940 severe curve |
10–18 years Females: 1763 (94.7%) Males: 97 (5.3%) |
Japanese | NS | Severe curve: 54.8° ± 12.1° Mild curve: 24.4° ± 4.0° |
NS | -Severe curve: Cobb angle of 40) -mild curve: Cobb angle <30. |
Peripheral blood sample | PCR-RFLP | LBX1 (ladybird homebox 1) 10q24.31 SNP rs11190870 |
No significant differences were observed between the groups |
Y. Takashi
(2018) |
| Retrospective case-control study (III) | 319 AIS patients 201 age-matched female healthy controls |
AIS patients: 14.3 ± 2.2; 10–16 Controls: 13.7 ± 1.2; 10–16 |
Chinese | major right thoracic curvature and major non-thoracic curvatures |
Cobb >10° | Until skeletal maturity or surgery | -Progressive curve group: Cobb >40° -non-progressive curve group: Cobb angle <40 |
Peripheral blood samples | PCR-RFLP | LBX1, BNC2, SOX9/KCNJ2, GPR126, AJAP4, BCL-2, PAX3/ EPHA4, LBX1 (LBX1- AS1). SNPs: rs11190870, rs12946942, rs13398147, rs241215, rs3904778, rs6570507, and rs678741 |
There was no association found between the seven SNPs with curve progression in AIS |
G. Man
(2018) |
| Prospective Case-control study (III) | 92 AIS patients: -50 patients in the progression group -42 patients in the non-progression group 276 unrelated subjects: -112 in progression group -164 in non-progression group |
AIS patients: -Progression group: 13.7 ± 2.4 Female: 37 (74%); Male: 13 (26%) -Non progression group: 13.3 ± 1.9 Female: 30 (71%); Male: 12 (29%) Unrelated subjects: -Progression group: 14.1 ± 2.1 Female: 85 (76%); Male: 27 (24%) -Non progression group: 13.8 ± 2.7 Female: 126 (76.8%) Male: 38 (23.2%) |
Chinese | Single thoracic, thoracolumbar, single lumbar, double thoracic, and double lumbar |
AIS patients: -Progression group curve > 45° -Non-progression group curve <30° Unrelated subjects: 10° < curve > 25° |
Until skeletal maturity | curve progression of at least 5° in two successive clinical follow-ups |
Peripheral blood sample | Oligonucleotide Ligation and Detection system |
The genome and methylome of peripheral monocytes were sequential | Methylation levels of site Cg01374129 (Has2 gene) were significantly lower in the progression group than in the non-progression group. |
Y. Meng
(2018) |
| Retrospective case-control study (III) | AIS patients: 13 Non-AIS controls: 10 |
AIS patients: 15.54 ± 1.76 Non-AIS patients: 15.60 ± 5.77 |
Chinese | NS | AIS patients: 58.15° ± 11.41° |
NS | NS | Human bone-derived primary bone cells from iliac crest bone tissue and serum | RT quantitative PCR | MiR-145 of Wnt/ß catenin | Significant negative correlations between circulating miR-145 and serum sclerostin, osteopontin, and osteoprotegerin. |
J. Zhang
(2018) |
| Retrospective case-control study (III) | 50 patients with AIS 50 healthy controls |
AIS patient: 12.98 ± 1.46 Female: 46 (92%) Male: 4 (8%) Healthy controls: 12.46 ± 1.59 Female: 45 (90%) Male: 5 (10%) |
Chinese | NS | 29 AIS patients > 40° 21 AIS patients < 40° |
NS | NS | Peripheral blood sample | PCR and pyrosequencing | COMP gene promoter methylation | AIS patients with different levels of methylation showed significant differences in Cobb angle of main curve (p = 0.011) |
S. Mao
(2018) |
| Retrospective Case-control study (III) | I960 AIS patients 1499 healthy subjects |
AIS group: 14.3 ± 3.2 Healthy group: 22.5 ± 5.9 |
Chinese | All AIS patients had main thoracic curve | AIS patients: 38.58 ± 12.38 | NS | NS | Peripheral blood samples Intraoperative muscular tissue |
RT-PCR | FBN 1 & FBN 2 106 SNPs of FBN 1 & FBN2 |
The expression level of FBN1 was remarkably correlated with the curve severity (p.0.02). |
F. Sheng
(2018) |
| Retrospective Case-control study (III) | 50 patients with AIS 50 healthy controls |
AIS patients: 22 patients: 10–13 28 patients: 14–16 Female: 46 (92%) Male: 4 (8%) |
Chinese | Thoracic or thoraco-lumbar curve | Cobb from 10° to 50° | NS | NS | Peripheral blood sample | Pyrosequencing | PITX1 PITX1 promoter methylation |
The methylation level of 6 CpG sites in PITX1 promoters was significantly associated with Cobb angle. |
B. Shi
(2018) |
| Retrospective Case-control study (III) | 5 AIS patients: -10 paraspinal muscle samples 60 Validation non-AIS patients |
AIS patients: -14.2 ± 1.92 years -5 female (100%) Validation non-AIS patients: -15.25 ± 2.64 -49 female (81.6%) -11 male (19.4%) |
Chinese | AIS patients: -Lenke 1: 3 -Lenke 3: 1 -Lenke 4: 1 Validation non- AIS patients: -Lenke 1: 34 -Lenke 2: 3 -Lenke 3: 15 -Lenke 4: 8 |
AIS patients: 56.8° ± 6.06° Validation non- AIS patients: 54.48° ± 10.09° |
NS | NS | Intraoperative paraspinal muscular samples | RNA sequences + Quantitative RT-PCR | ADIPOQ mRNA and H19 mRNA | ADIPOQ mRNA and H19mRNA showed statistical significance (p < 0.001 and p = 0.04, respectively) |
H. Jiang
(2018) |
| Retrospective Case-control study (III) | 100 AIS patients: -53 progressive curves -47 non-progressive curves 100 healthy controls |
AIS patients: 12.7 ± 1.5 Female: 100 (100%) Healthy controls: Female: 100 (100%) |
Polish | Right-sided thoracic curve of Cobb angle greater than 20° (Lenke types 1 and 3). | AIS patients: -Whole group: 31.3° -Progression group: 35.4 -Non-progression group: 27.7 |
34.8 ± 21.6 | More than 12° of Cobb angle every year | Peripheral blood sample | PCR-FRET | TIMP2 Nine different TIMP2 polymorphism |
Four of the polymorphisms showed non-equal distributions in patients with different progression rates. |
M. Andrusiewicz
(2019) |
| Retrospective Case-control study (III) | 223 AIS patients 375 age-matched controls |
AIS patients: 127 patients < 12 96 patients > 12 Female:199 (89%) Male: 24 (11%) |
Chinese | Lenke 1: 23 Lenke 2: 110 Lenke 3: 28 Lenke 4: 27 Lenke 5: 29 Lenke 6: 6 |
130 patients < 23° 93 patients > 23° |
11.9 (1.4 months to 31 months) | a curve greater than 30° after skeletal maturity was used to define curve progression |
Peripheral blood sample | Exome sequencing | The authors searched for rare damaging variants (defined as missense, nonsense, frameshift, or splice-site variants and variants with a minor allele frequency of <1% in public databases) |
The number of rare damaging variants associated with curve progression (p < 0.05, OR = 4.304, 95%, CI 2.4 to 7.5 |
H. Jiang
(2019) |
| Retrospective Cohort study (II) |
2272 patients with severe AIS 13,859 healthy controls |
NS | Japanese; Chinese and Scandinavian | NS | NS | NS | NS | Peripheral blood or saliva sample | PCR based | 17q24.3 near the genes SOX9 and KCNJ2) rs12946942 |
rs12946942 SNP showed significant association in severe AIS patients: |
K. Takeda
(2019) |
| Retrospective Case-Control study (III) | 50 AIS patients 50 Healthy controls |
AIS patients: -12.6 ± 1.5 years (10–18 years) Healthy controls: -12.5 ± 1.6 years (10–18 years) 100 females (100%) |
Chinese | NS | AIS patients: -20.1° ± 8.3° (10°–60°) |
12 months | NS | Peripheral blood samples | RT-PCR | PCDH10 gene methylation and expression | PCDH10 methylation level significantly correlated to curve severity | B. Shi (2019) |
| Retrospective Case-control study (III) | (1) mi-RNA sequencing cohort: 10 AIS patients: -5 severe curves -5 mild curves 5 Healthy controls (2) qPCRT validation cohort: -40 severe curve -40 mild curve -40 healthy controls (3) Facet joints and bone tissues group: -21 severe AIS patients -20 non-scoliosis patients |
Mi RNA sequence cohort: -Severe AIS: 13.0 ± 2.5 years 5 female (100%) -Mild AIS: 14.2 ± 0.8 years 5 female (100%) -5 controls: 11.6 ± 2.9 years 5 female (100%) qPCR cohort: -Severe AIS: 12.6 ± 2.2 years 27 females (67.5%) 13 males (32.5%) -Mild AIS: 12.4 ± 1.8 years 30 female (75%) 10 males (25%) -Healthy controls: 12.2 ± 1.9 28 female (70%) 12 male (30%) |
Chinese | NS | Mi RNA sequence cohort: -Severe AIS: 64.6° ± 16.7° -Mild AIS: 26.0° ± 5.8° qPCR cohort: -Severe AIS: 61.3° ± 9.5° -Mild AIS: 22.7° ± 6.7° |
NS | NS | Peripheral blood sample and bone tissue | RT-PCR | miR-151a-3p and GREM1 expression | miR-151a-3p and GREM1 expression significantly correlated to severe AIS curves | Y. Wang (2020) |
| Retrospective case series (IV) | 211 AIS patients: -Non-progressive curve = 80 -Slowly progressive curve = 78 -Rapidly progressive curve = 53 83 healthy subjects |
AIS patients: -Non-progressive: 18.5 ± 1.8 (15.0–24.1) -Slowly progressive: 16.9 ± 2.4 (15–26.2) -Rapidly progressive:16.3 ± 7.1 (12.4–50.1) Female: 211 (100%) |
Caucasian | NS | AIS patients: -Non-progressive: 23.9 ± 5.4 (10–30) -Slowly progressive: 38.9 ± 7.9 (30–65) -Rapidly progressive: 62.7 ± 15.7 (39–114) |
12 months |
The change of Cobb angle value on the two consecutive X-rays taken at 12-month time intervals expressed in degrees per month. |
Peripheral blood sample | PCR-RFLP for: rs1017861, rs1324842, rs4738813 Sanger sequencing for: rs78874766 rs4738824, rs7479761 |
CHD7 rs1017861, rs13248429, rs4738813 rs78874766, rs4738824, and rs74797613. |
rs1017861 and rs4738813 were associated with curve severity and progression rate (p < 0.05). |
K. Borysiak
(2020) |
| Retrospective case-control study (III) | 1952 AIS patients: -747 progression group -520 non-progression group 2495 healthy controls |
AIS group: -Progression group: 13.2 ± 2.4 -Non progression group: 13.0 ± 2.3 Female: 1952 (100%) |
Chinese |
-1218 (62.4%) main thoracic curve -476 (24.3%) double major curve -258 (13.3%) major lumbar curves |
36.8 ± 3.2, (22–66) | NS |
Progression group: -Cobb angle >50° and Risser grade < 3 Non-progression group: -Cobb angle < 30° and Risser grade >3 at final follow-up |
Peripheral blood sample 76 intraoperative muscular tissue |
RT-PCR | MIR4300 HG gene rs35333564 |
Significant difference between two groups regarding both genotype frequency and minor allele frequency of rs35333564 in MIR4300 gene. |
Y. Wang
(2021) |
| Retrospective case series (IV) | 8 female monozygotic twin pairs (n = 16 patients): -6 discordant twin pairs (difference in primary curve Cobb angle > 10°) -2 concordant twin pairs (difference in primary curve < 2°) |
All individuals: -37.3 ± 22.5 years Female: 16 (100%) |
Caucasian | NS | 39.6° ± 15.3° | NS | NS | Peripheral blood sample | Microarray analysis | Genome-wide methylation in blood (Differentially methylation region (DMR) promoter enrichment analyses) | SNPs hypomethylation associated with curve severity |
P. Carry
(2021) |
| Retrospective case series (IV) | 29 AIS surgery patients: -10 patients with Cobb ≤70° -19 patients with Cobb >70° |
All individuals: 14.5 ± 1.5 years (12.1–17.9) 29 female (100%) |
Caucasian | Main thoracic curve | All individuals: 77.4° ± 16.1° (52°–115°) |
2 years | NS | Intraoperative deep paraspinal muscles sample and trapezius muscles | PRC and Pyrosequencing | Methylation levels of ESR1 regulatory regions | DRM1/2 methylation status was significantly associated with curve severity | P. Janusz (2021) |