The vitamin D receptor TaqI TT genotype is associated with type 1 diabetes in the Black South African population.

Polymorphisms in the vitamin D receptor (VDR) gene (BsmI (rs1544410), FokI (rs2228570), ApaI (rs7975232), TaqI (rs731236)) and low vitamin D concentrations have previously been associated with type 1 diabetes (T1D). Vitamin D is thought to mediate the switch from a pro-inflammatory Th1 response to an anti-inflammatory Th2 response which is protective against the development of T1D. These associations are inconsistent across studies and population groups. These associations have not been investigated in the South African black population. Thus, this observational, case-control study aims to address this knowledge gap. South African black participants with T1D (cases; n = 182) and healthy controls (n = 151) were genotyped for the four VDR polymorphisms using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Vitamin D levels were measured using high performance liquid chromatography (HPLC). Vitamin D levels were not significantly different between cases and controls (62.8 ± 20.7 vs. 59.5 ± 17.0 nmol/l, respectively; P = 0.122). Higher vitamin D levels were associated with the TaqI TT (P = 0.045) and FokI TT/TC (P = 0.014) genotypes in multivariate analyses. Furthermore, the TaqI TT genotype was associated with T1D status in multivariate analysis (P = 0.040). The FokI CC genotype increases the transcription of CYP24A1, resulting in vitamin D catabolism and thus decreased vitamin D concentration through the action of 24-hydroxlase. The TaqI TT genotype results in increased vitamin D potentially through calcium metabolism feedback pathways. In addition, the TaqI TT genotype is associated with T1D through a vitamin D-independent mechanism and may be in linkage disequilibrium with a true causative variant.