Polymorphisms in Vitamin A-Related Genes and Their Functions in Autoimmune Thyroid Disease
Polymorphisms in Vitamin A-Related Genes and Their Functions in Autoimmune Thyroid Disease
复制标题
DOI：
10.1089/thy.2021.0312
复制
发表时间：
2021-10-26
期刊：
影响因子：
6.6
通讯作者：
Iwatani, Yoshinori
中科院分区：
文献类型：
--
作者：
Homma, Hinako;Watanabe, Mikio;Iwatani, Yoshinori
背景：维生素A是一种抑制免疫反应的因子，包括辅助性T细胞（Th）1和Th 17反应。然而，目前还没有报道表明维生素A相关基因（CYP 26 B1，RARB和RARG）与自身免疫性甲状腺疾病（AITD）的预后之间的关联。本研究的目的是澄清维生素A相关基因和AITD.Methods的易感性和预后之间的关联：我们使用聚合酶链反应-限制性片段长度多态性方法基因型多态性编码维生素A相关分子的基因。用流式细胞术分析辅助性T细胞的比例。结果：轻度桥本氏甲状腺炎（HT）患者的CYP 26 B1 rs3768641 GG基因型和G等位基因频率显著高于重度HT患者（p = 0.0013和0.0024）。RARB rs 1997352 CC基因型在HT患者中的频率显著高于对照组（p = 0.0207）。Th 17细胞比例在CYP 26 B1 rs 2241057 TT基因型中显著高于C携带者（CC+CT基因型）（p=0.0385），在RARB rs 1997352 A携带者（AA+AC基因型）中显著高于CC基因型（p = 0.0246），在RARG rs7398676 G携带者（GG+GT基因型）中显著高于TT基因型（p = 0.0249）。在RARB rs 1997352多态性中，具有高浓度IFN-γ（>= 150 ng/mL）的HT患者在CC基因型中比A携带者（AA+AC基因型）更常见（p = 0.0226）。在具有CYP 26 B1 rs 2241057单核苷酸多态性（SNP）的TT基因型（p = 0.0026）和具有CYP 26 B1 rs3798641 SNP的GG基因型（p = 0.030）的受试者中，IL-17的血清水平显著升高。RARG 7398676 G基因型（GG+GT基因型）中IL-17浓度>= 0.71 pg/mL的受试者比TT基因型的受试者更常见（p= 0.0218）。结论：CYP 26 B1基因多态性与Th 17细胞比例、IL-17水平和HT严重程度相关。RAR基因多态性与Th 17细胞比例、IFN-γ和IL-17浓度以及HT易感性相关。
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)-gamma 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-gamma (>= 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-gamma and IL-17, and susceptibility to HT.