Polymorphisms in vitamin A-related genes and their functions in autoimmune thyroid disease.

Background Vitamin A is a factor that suppresses immune responses, including Th1 and Th17 responses. However, there has been no report showing the association between vitamin A-related genes (CYP26B1, RARB and RARG) and the prognosis of autoimmune thyroid disease (AITD). To clarify the association between vitamin A-related genes and the susceptibility and prognosis of AITD. Methods We genotyped polymorphisms in genes encoding vitamin A-related molecules using the PCR-RFLP method. The proportion of T helper cells was analyzed by flow cytometry. Serum interleukin (IL)-17 and interferon (IFN)-γ were examined by ELISA. Results CYP26B1 rs3768641 GG genotype and G allele were significantly more frequent in patients with mild HT than in those with severe HT (P=0.0013 and 0.0024, respectively). The RARB rs1997352 CC genotype was significantly more frequent in HT patients than in controls (P=0.0207). The proportion of Th17 cells was significantly higher in CYP26B1 rs2241057 TT genotype than C carrier (CC+CT genotypes) (P=0.0385), in RARB rs1997352 A carrier (AA+AC genotypes) than those with CC genotype (P=0.0246), and in RARG rs7398676 G carrier (GG+GT genotypes) than in TT genotype (P=0.0249). In the RARB rs1997352 polymorphism, HT patients showing a high concentration of IFN-γ (≧150ng/ml) were more frequent in the CC genotype than in A carriers (AA+AC genotypes) (P=0.0226). Serum levels of IL-17 were significantly elevated in subjects with the TT genotype of the CYP26B1 rs2241057 SNP (p=0.0026) and in subjects with the GG genotype of the CYP26B1 rs3798641 SNP (P=0.030). Subjects showing a high concentration of IL-17 (≥0.71pg/ml) were more frequent in RARG 7398676 G carriers (GG+GT genotypes) than in TT genotype (P=0.0218). Conclusions Polymorphisms on the CYP26B1 gene were related to the proportion of Th17 cells, the level of IL-17 and the severity of HT. Polymorphisms on RAR were related to the proportion of Th17 cells, concentrations of IFN-γ and IL-17, and susceptibility to HT.