Table 4.
Vitamin D receptor gene (VDR) variants in South Africans, associated with ethnicity, disease, treatment response, DNA methylation, VDR expression, vitamin D receptor protein (VDR) level or VDR transactivation of target genes.
| SNP (rs) | Study Population; Gender when Specified | Factor Investigated | Study Design | Median/Mean Age, Years (Range) | Association | Reference |
|---|---|---|---|---|---|---|
|
FokI (rs2544037) (rs10783219) (rs10735810) TaqI (rs731236) |
22 male, 28 female Cape mixed; 26 male, 24 female Black Africans (Zhosa) | Determinants of 25(OH)D status, before and after vitamin D supplementation | Longitudinal | (18–24) | FokI (rs10735810) “AG” contributed to lower 25(OH)D, and lower 25(OH)D in winter and post-supplementation, while “AA” contributed to higher 25(OH)D, in a linear model incorporating UVB exposure, skin pigmentation, ethnicity, age and sex | [38] |
|
ApaI (rs7975232) TaqI (rs731236) |
264 Black Africans, 247 Whites, 194 Asian-Indians | Ethnicity | Retrospective cross-sectional cohort of healthy male and female blood donors | NA | Higher ApaI “AA” and TaqI “TT” in Blacks than Whites or Asian-Indians; no difference between Whites and Asian-Indians. Higher frequency of TaqI “T” may contribute to lower incidence of osteoporosis in Blacks | [85] |
|
FokI (rs2228570) BsmI (rs1544410) ApaI (rs7975232) TaqI (rs731236) |
95 Black Africans (Venda) with TB, 117 ethnicity matched controls | TB | Case-control | NA | No independent SNP association; FokI-BsmI-ApaI-TaqI haplotype “F-b-A-T” (C-G-T-T) protects | [86] |
|
FokI (rs2228570) ApaI (rs7975232) TaqI (rs731236) |
All Colored: 249 TB cases, 352 ethnicity matched controls, 220 TB cases converting from positive to negative |
TB and chemotherapy for TB | Case-control for TB; longitudinal for TB conversion | (18–65) | No association of VDR allele, genotype, haplotype or diplotype with TB. Quicker response to TB chemotherapy in ApaI “AA” (TT) vs. “aa” (GG), in TaqI “Tt” (TC) vs. “tt” (CC) and in TaqI “TT” (TT) vs. “tt” (CC) | [87] |
|
ApaI (rs7975232) TaqI (rs731236) |
15 male, 15 female CAU (North America); 15 male, 15 female YRI (Nigeria); 16 male, 16 female Black Africans (Venda) with TB together with 12 male and 17 female healthy Black African controls | Ethnicity, TB, and DNA methylation of the VDR 3’ region CGI 1060 | Ethnicity; case-control for TB | CAU 32 (22–44), YRI unknown, TB cases 38 (18–62) TB controls 34 (21–62) |
Methylation variable positions in 3’ end of VDR distinguish ethnicity and TB status. Higher regional methylation in TaqI “TC/CC” than “TT” in YRI and Venda, but not in CAU | [88] |
| FokI (rs10735810 merged into rs2228570) | 296 Black Africans with RSV, 113 Black African controls | RSV-related disease | Case-control | Cases 3.0 months, controls 3.5 months |
FokI “C” frequency higher in Black South Africans than European, Asian and Japanese populations. “CT” and “T” predispose to RSV disease, while “CC” protects | [89] |
| FokI (rs2228570) | 40 healthy Black Africans, 20 healthy Whites | VDR expression and VDR function, considering ethnicity and 25(OH)D levels | Cross-sectional cohort of male and female blood donors | 35 (17–65) | Higher frequency FokI “CC” genotype and VDR protein in Blacks than Whites, but less VDR mRNA and CAMP mRNA. CAMP mRNA higher in FokI “CT/TT” genotypes than “CC”. Circulating 25(OH)D levels ≥50 nmol/L, and comparable between Blacks and Whites. Different effects on CAMP and CYP24A1 expression in Whites and Blacks on supplementation with 1,25(OH)2D | [90] |
1,25(OH)2D: 1,25-Dihydroxyvitamin D; 25(OH)D: 25-Hydroxyvitamin D; CAMP: Gene coding cathelicidin antimicrobial protein; CAU: Caucasian; CGI: CpG island; CYP24A1: Gene coding cytochrome P450 family 24 subfamily A member 1; NA: Not available; RSV: Respiratory syncytial virus; SNP (rs): Single nucleotide polymorphism (reference SNP cluster ID to access a specific SNP in the dbSNP database); TB: Tuberculosis; UVB: Ultraviolet B radiation; YRI: Yoruba (African ancestry, Ibadan, Nigeria).