Vitamin D has immunomodulatory effects, and its deficiency has been implicated in the autoimmune process of type 1 diabetes. Serum vitamin D levels are influenced by variants in genes involved in the synthesis, transport, hydroxylation and degradation of vitamin D. The aim of this study was to assess if single nucleotide polymorphisms (SNPs) at the DHCR7 (rs12785878), GC (rs2282679), CYP2R1 (rs2060793) and CYP24A1 (rs6013897) loci are associated with type 1 diabetes in the Portuguese population. Genotype and allele frequencies were determined in 350 cases of type 1 diabetes and in 490 controls. The frequency of each SNP alone was not significantly different between patients and controls. However, the combined analysis of the four SNPs showed that minor alleles of these variants clustered more frequently in patients. The proportion of individuals with three or more minor alleles was significantly higher in patients than in controls (56.3% vs. 48.5; odds ratio (OR) 1.37; 95% confidence interval (CI) 1.04–1.81; p-value 0.027). These results suggest a cumulative effect of SNPs at the DHCR7, GC, CYP2R1 and CYP24A1 loci on the susceptibility to type 1 diabetes, due to the roles of these genes in the vitamin D metabolic pathway.

中文翻译：

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维生素 D 通路遗传变异和 1 型糖尿病：病例对照协会研究

维生素 D 具有免疫调节作用，其缺乏与 1 型糖尿病的自身免疫过程有关。血清维生素 D 水平受参与维生素 D 合成、转运、羟基化和降解的基因变异的影响。 本研究的目的是评估 DHCR7 (rs12785878)、GC (rs2282679) 的单核苷酸多态性 (SNP) 、CYP2R1 (rs2060793) 和 CYP24A1 (rs6013897) 基因座与葡萄牙人群中的 1 型糖尿病相关。在 350 名 1 型糖尿病患者和 490 名对照组中确定了基因型和等位基因频率。每个 SNP 的频率在患者和对照之间没有显着差异。然而，对四个 SNP 的综合分析表明，这些变异的次要等位基因在患者中更频繁地聚集。患者中具有三个或更多次要等位基因的个体比例显着高于对照组（56.3% 对 48.5；优势比 (OR) 1.37；95% 置信区间 (CI) 1.04–1.81；p 值 0.027）。这些结果表明，由于这些基因在维生素 D 代谢途径中的作用，DHCR7、GC、CYP2R1 和 CYP24A1 位点的 SNP 对 1 型糖尿病的易感性具有累积效应。