Polymorphisms in Vitamin A-Related Genes and Their Functions in Autoimmune Thyroid Disease.

Abstract

Background: Vitamin A is a factor that suppresses immune responses, including T helper (Th)1 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). The objective of this study was 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 polymerase chain reaction-restriction fragment length polymorphism method. The proportion of T helper cells was analyzed by flow cytometry. Serum interleukin (IL)-17 and interferon (IFN)-γ were examined by enzyme-linked immunosorbent assay. Results:CYP26B1 rs3768641 GG genotype and G allele were significantly more frequent in patients with mild Hashimoto's thyroiditis (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 with a high concentration of IFN-γ (≥150 ng/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 single nucleotide polymorphism (SNP) (p = 0.0026) and in subjects with the GG genotype of the CYP26B1 rs3798641 SNP (p = 0.030). Subjects with a high concentration of IL-17 (≥0.71 pg/mL) were more frequent in RARG 7398676 G carriers (GG+GT genotypes) than in TT genotype (p = 0.0218). Conclusions: Polymorphisms in the CYP26B1 gene were related to the proportion of Th17 cells, the level of IL-17 and the severity of HT. Polymorphisms in RAR were related to the proportion of Th17 cells, concentrations of IFN-γ and IL-17, and susceptibility to HT.