Genetic polymorphisms of vitamin D receptor gene and the risk of Hashimoto's thyroiditis: an Iraqi case-control study

Abstract

Abstract Background Recently, the vitamin D receptor gene polymorphisms has been linked to various autoimmune diseases. The key aim of this study is to explore the association between VDR gene polymorphisms (rs2228570, rs1544410, rs731236, rs7975232) and the risk of Hashimoto's thyroiditis (HT) among the Iraqi population. Methods Peripheral blood samples were used to isolate genomic DNAs from 180 HT patients and 200 healthy controls. Four VDR gene loci were amplified, and the obtained amplicons were then digested using the restriction enzymes FokI, BsmI, TaqI and ApaI. The digested fragments were then electrophoresed on agarose gel (2.5%). HT polymorphisms and estimated haplotypes were computed by odds ratios (ORs). Results After stratification by age, gender and body mass index (BMI), univariate logistic regression statistical analysis revealed a significantly higher incidence of FokI (rs2228570) polymorphisms in HT patients compared to healthy controls. In contrast, the incidence of the BsmI (rs1544410) and TaqI (rs731236) polymorphisms were significantly higher in healthy controls than in the HT patient group. Linkage disequilibrium (LD) analysis of pairs of SNPs revealed that the polymorphisms in the VDR gene (rs731236 A/G and rs7975232 G/C) were in strong LD in an HT model (D’= 0.86). Furthermore, AAGC and AAGT haplotype models (OR = 1.50, 95% CI: 1.09 − 2.07; OR = 1.61, 95% CI: 1.06 − 2.45, P = 0.02) were associated with an increased risk of HT, while the AACC haplotype model (OR = 0.37, 95% CI: 0.15–0.90, P = 0.02) exhibited a significantly decreased the risk of developing HT. Conclusion Our research supports the association between HT and the FokI polymorphism among the Iraqi population. In addition, the haplotype analysis reveals that the combination of mutant alleles from several VDR gene polymorphisms makes these individuals more susceptible to HT.