Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, Poznan, Poland.
Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.
Endocrine. 2021 Oct;74(1):72-79. doi: 10.1007/s12020-021-02743-9. Epub 2021 May 8.
Genetically predisposed individuals may develop several autoimmune diseases-autoimmune polyendocrine syndromes (APS). APS types 2-4, are complex disorders, which combine various organ-specific autoimmune conditions. Recent reports support the considerable role of the BACH2 gene in immune cell differentiation and shifting the T-cell balance towards regulatory T-cells. BACH2 polymorphisms are associated with autoimmune disorders, including Addison's disease (AD), Graves' disease (GD), and probably type 1 diabetes (T1D). Our study was aimed to investigate the BACH2 variant, rs3757247, in endocrine autoimmunity in the Polish population.
The analysis comprised 346 individuals with APS, 387 with T1D only, and 568 controls. Genotyping was performed using TaqMan chemistry.
APS type 2 was found in 219 individuals, type 3 in 102, and type 4 in 25 subjects. Overall, AD was diagnosed in 244 subjects, Hashimoto's thyroiditis-in 238, T1D-in 127, GD-in 58, vitiligo and chronic gastritis each in 40 patients, celiac disease-in 28, premature menopause in 18, and alopecia in 4 patients. Minor T allele at rs3757247 was found in 56.4% APS vs. 44.1% control alleles (OR 1.59; 95%CI: 1.30-1.95, p < 0.0001). The distribution of genotypes revealed excess TT homozygotes in the APS cohort (33.2 vs. 20.1% in controls, p < 0.0001). The frequencies of rs3757247 alleles and genotypes in T1D patients did not present significant differences vs. controls (p-values > 0.05).
These results provide evidence of the association between BACH2 polymorphism and polyglandular autoimmunity. Since carriers of rs3757247 display increased risk for additional autoimmune conditions, this variant could identify individuals prone to develop APS.
遗传易感性个体可能会患上多种自身免疫性疾病——自身免疫性多内分泌腺综合征（APS）。APS 类型 2-4 是复杂的疾病，它们结合了各种特定器官的自身免疫性疾病。最近的报告支持 BACH2 基因在免疫细胞分化和向调节性 T 细胞转移 T 细胞平衡方面的重要作用。BACH2 多态性与包括 Addison 病（AD）、Graves 病（GD）和可能的 1 型糖尿病（T1D）在内的自身免疫性疾病有关。我们的研究旨在调查 BACH2 变体 rs3757247 在波兰人群内分泌自身免疫中的作用。
该分析包括 346 名 APS 患者、387 名仅患有 T1D 的患者和 568 名对照者。使用 TaqMan 化学法进行基因分型。
219 名患者为 APS 2 型，102 名患者为 APS 3 型，25 名患者为 APS 4 型。总的来说，244 名患者被诊断为 AD，238 名患者为桥本甲状腺炎，127 名患者为 T1D，58 名患者为 GD，40 名患者为白癜风和慢性胃炎，28 名患者为乳糜泻，18 名患者为早发性绝经，4 名患者为脱发。rs3757247 的次要 T 等位基因在 APS 中为 56.4%，而在对照组中为 44.1%（OR 1.59；95%CI：1.30-1.95，p<0.0001）。基因型分布显示 APS 队列中 TT 纯合子过多（33.2%比对照组中的 20.1%，p<0.0001）。T1D 患者的 rs3757247 等位基因和基因型频率与对照组相比无显著差异（p 值>0.05）。
这些结果提供了 BACH2 多态性与多腺体自身免疫之间存在关联的证据。由于 rs3757247 的携带者发生其他自身免疫性疾病的风险增加，因此该变体可以识别易患 APS 的个体。
