The functional polymorphisms of VDR , GC and CYP 2 R 1 are involved in the pathogenesis of autoimmune thyroid diseases

Summary Vitamin D is a multi‐functional immune regulator, and a low serum concentration of vitamin D promotes autoimmune inflammation. In this study, we evaluate the association between the prognosis of autoimmune thyroid disease ( AITD ) and the functional polymorphisms of genes that regulate vitamin D metabolism. For 139 G raves’ disease ( GD ) patients, 116 H ashimoto's disease ( HD ) patients and 76 control subjects, we genotyped the following polymorphisms using polymerase chain reaction–restriction fragment length polymorphism ( PCR – RFLP) : vitamin D receptor ( VDR ): rs731236, rs7975232, rs2228570 and rs1544410; group‐specific component ( GC ): rs7041 and rs4588; and CYP 2 R 1: rs10741657. The frequency of the TT genotype for the rs731236 polymorphism was higher in GD patients than in HD patients ( P  = 0·0147). The frequency of the C allele for the rs7975232 polymorphism was higher in GD patients than in control subjects ( P  = 0·0349). The proportion of GD patients whose anti‐thyrotrophin receptor antibody ( TRAb ) level was >51% was higher in those with the CC genotype than in those with the CA + AA genotypes ( P  = 0·0065). The frequency of the CC genotype for the rs2228570 polymorphism was higher in HD patients than in control subjects ( P  = 0·0174) and GD patients ( P  = 0·0149). The frequency of the Gc 1 Gc 1 genotype for the GC polymorphism and the AG genotype for the CYP 2 R 1 polymorphism were lower in intractable GD than in GD in remission ( P  = 0·0093 and 0·0268, respectively). In conclusion, genetic differences in the VDR gene may be involved in the development of AITD and the activity of GD , whereas the genetic differences in the GC and CYP 2 R 1 genes may be involved with the intractability of GD .