Vitamin D Pathway Genetic Variation and Type 1 Diabetes: A Case–Control Association Study

Abstract

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.

Progress in the Relationship between Vitamin D Deficiency and the Incidence of Type 1 Diabetes Mellitus in Children

“…CYP2R1 rs12794714 and rs10766196 polymorphisms were associated with a high risk of T1DM, and polymorphisms in vitamin D metabolism could lead to susceptibility to T1DM in Korean children [60]. Another similar study showed a cumulative effect of SNPs at the CYP2R1 (rs2060793), DHCR7 (rs12785878), GC (rs2282679), and CYP24A1 (rs6013897) loci on the susceptibility to type 1 diabetes [61]. Tangjittipokin et al [62] found SNPs and T1DM in CYP2R1 (rs10741657) (GA, OR: 1.83, 95% CI: 1.01-3.31; p = 0:04).…”

An Update on the Effects of Vitamin D on the Immune System and Autoimmune Diseases

“…On the other hand, one mendelian randomization study including single nucleotide polymorphisms (SNPs) that are associated with 25(OH)D levels included in a large vitamin D genome-wide association study (GWAS) on more than 400,000 Europeans demonstrated that 25(OH)D levels were unlikely to present an impact on the risk of developing T1D [ 214 , 233 ]. Another case-control study did not register a significant association of each SNP (DHCR7, GC, CYP2R1 and CYP24A1 genes) with T1D but demonstrated a combined effect of multiple risk alleles [ 214 , 234 ].…”

The impact of genetic variants related to vitamin D and autoimmunity: A systematic review

“…In patients, the TT genotype of the rs2228570 variant showed higher levels of 25(OH)D compared to CC + TC in the same polymorphism. Type 1 Diabetes Almeida, J 2020 [ 213 ] Portugal Case-Control 350/490 29 ± 11.1/32,2 ± 11.2 PCR-RFLP and TaqMan Genotyping Assay Sex and age DHCR7, GC, CYP2R1 and CYP24A1 DHCR7 (rs12785878), GC (rs2282679), CYP2R1 (rs2060793) and CYP24A1 (rs6013897) The frequency of each SNP alone was not significantly different between patients and controls. However, was observed a cumulative effect of minor alleles of SNPs at the DHCR7, GC, CYP2R1 and CYP24A1 loci on the susceptibility to type 1 diabetes.…”