Estrogen receptor alpha dinucleotide repeat polymorphism in Japanese patients with autoimmune thyroid diseases

BACKGROUND: The autoimmune thyroid diseases (AITDs), comprising Graves' disease (GD) and Hashimoto's thyroiditis (HT), appear to develop as a result of complex interactions between predisposing genes and environmental triggers. Susceptibility to AITDs is conferred by genes in the human leukocyte antigen (HLA) and genes unlinked to HLA, including the CTLA-4 gene. Recently, an association to some estrogen receptor (ER)α genotypes with breast cancer, hypertension, osteoporosis, generalized osteoarthritis, and some autoimmune diseases such as rheumatoid arthritis has been reported. We have analyzed a dinucleotide (TA)n repeat polymorphism lying upstream of the human ERα gene in patients with AITDs and in normal subjects. RESULTS: Seventeen different alleles were found in 130 patients with GD, 93 patients with HT, and 190 control subjects. There was no significant difference in the distributions of ERα alleles between patients and controls. CONCLUSIONS: The present results do not support an association between the ERα gene and AITD in the Japanese population.

背景：自身免疫性甲状腺疾病（autoimmune thyroid diseases, AITDs）包括格雷夫斯病（Graves' disease, GD）与桥本甲状腺炎（Hashimoto's thyroiditis, HT），其发生源于易感基因与环境诱因的复杂相互作用。自身免疫性甲状腺疾病的易感性由人类白细胞抗原（human leukocyte antigen, HLA）基因及与HLA非连锁的基因（包括细胞毒性T淋巴细胞相关抗原4（CTLA-4）基因）所介导。近期有研究报道，部分雌激素受体（estrogen receptor, ER）α基因型与乳腺癌、高血压、骨质疏松症、全身性骨关节炎以及类风湿关节炎等部分自身免疫性疾病存在关联。本研究针对自身免疫性甲状腺疾病患者及正常受试者，对人类ERα基因上游区域的二核苷酸（TA）n重复多态性进行了分析。
结果：本研究在130例格雷夫斯病患者、93例桥本甲状腺炎患者及190名正常对照者中共检出17种不同的等位基因。患者组与对照组的ERα等位基因分布无显著差异。
结论：本研究结果显示，在日本人群中，ERα基因与自身免疫性甲状腺疾病之间不存在关联。