Bhola Sureka, Cave Eleanor M, Prigge Katherine L, Bhana Sindeep, Crowther Nigel J, Padoa Carolyn J
Department of Chemical Pathology, National Health Laboratory Services (NHLS), Johannesburg, South Africa.
University of Witwatersrand, Johannesburg, South Africa.
J Nutr Sci. 2024 Nov 28;13:e73. doi: 10.1017/jns.2024.77. eCollection 2024.
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 , 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.
维生素D受体（VDR）基因（BsmI（rs1544410）、FokI（rs2228570）、ApaI（rs7975232）、TaqI（rs731236））多态性及低维生素D浓度此前已被发现与1型糖尿病（T1D）有关。维生素D被认为可介导从促炎性Th1反应向抗炎性Th2反应的转变，而这种转变对T1D的发生具有保护作用。这些关联在不同研究和人群组中并不一致。南非黑人人群中尚未对这些关联进行研究。因此，这项观察性病例对照研究旨在填补这一知识空白。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术对182例患有T1D的南非黑人参与者（病例组）和151例健康对照者进行了上述四种VDR多态性的基因分型。使用高效液相色谱法（HPLC）测量维生素D水平。病例组和对照组的维生素D水平无显著差异（分别为62.8±20.7与59.5±17.0 nmol/L；P = 0.122）。在多变量分析中，较高的维生素D水平与TaqI TT基因型（P = 0.045）和FokI TT/TC基因型（P = 0.014）相关。此外，在多变量分析中，TaqI TT基因型与T1D状态相关（P = 0.040）。FokI CC基因型会增加[此处原文缺失相关内容]的转录，导致维生素D分解代谢，从而通过24-羟化酶的作用降低维生素D浓度。TaqI TT基因型可能通过钙代谢反馈途径导致维生素D增加。此外，TaqI TT基因型通过一种不依赖维生素D的机制与T1D相关，可能与一个真正的致病变异处于连锁不平衡状态。
