Association and gene-gene interaction analyses for polymorphic variants in CTLA-4 and FOXP3 genes: role in susceptibility to autoimmune thyroid disease
Association and gene-gene interaction analyses for polymorphic variants in CTLA-4 and FOXP3 genes: role in susceptibility to autoimmune thyroid disease
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DOI：
10.1007/s12020-019-01859-3
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发表时间：
2019-06-01
期刊：
影响因子：
3.7
通讯作者：
Ishaq, Mohammed
中科院分区：
文献类型：
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作者：
Fathima, Nusrath;Narne, Parimala;Ishaq, Mohammed
细胞毒性T淋巴细胞抗原-4（CTLA-4）和叉头盒蛋白P3（FOXP 3）基因的多态性变体与免疫稳态失调和自身免疫性疾病有关。我们分析了CTLA-4 rs 231775和FOXP 3 rs3761548、rs3761549多态性与自身免疫性甲状腺疾病（AITD）易感性之间的关联，包括南印度人群中的桥本甲状腺炎（HT）和Graves病（GD），共355例AITD受试者用PCR-RFLP方法对275例HT和80例GD患者和285例年龄和性别匹配的对照者进行上述多态性的基因分型。与对照组相比，HT和GD受试者中等位基因占优势，并分别对HT（p = 0.009）和GD（p = 0.02）的易感性产生显性影响。rs3761548和rs3761549多态性与AITD易感性无等位基因关联，尽管rs3761549基因型分布存在显著差异。单倍型分析显示，rs3761548“C”-rs3761549“T”在HT和GD受试者中的频率增加，从而将其与疾病易感性相关联（p = 0.03）。多因素降维分析显示CTLA-4和FOXP 3基因在影响AITD易感性方面存在冗余，CTLA-4基因rs 231775多态性的遗传变异增加了HT和GD的易感性。此外，结合FOXP 3基因变异，它似乎分别影响HT和GD的易感性。结合抗甲状腺抗体筛查，这些发现的重要性可能有助于细致的病例发现，以有效治疗HT和GD。
Polymorphic variants of cytotoxic T-lymphocyte antigen-4 (CTLA-4) and forkhead box protein P3 (FOXP3) genes are implicated in dysregulated immune homeostasis and autoimmune disorders. We analyzed the association between CTLA-4 rs231775 and FOXP3 rs3761548, rs3761549 polymorphisms and predisposition to autoimmune thyroid disease (AITD), inclusive of Hashimoto's thyroiditis (HT) and Graves' disease (GD) in South-Indian population.A total of 355 AITD subjects (comprising 275 HT and 80 GD) and 285 randomly selected age- and sex-matched control subjects were genotyped for the aforementioned polymorphisms by PCR-RFLP method.The rs231775 "G" allele was preponderant in HT and GD subjects when compared with controls and exerted a dominant influence on the susceptibility to HT (p = 0.009) and GD (p = 0.02), respectively. There was no allelic association of rs3761548 and rs3761549 polymorphisms with AITD susceptibility, albeit a significant difference in genotype distribution with respect to rs3761549. Haplotype analysis revealed an increased frequency of rs3761548 "C"-rs3761549 "T" in HT and GD subjects, thereby associating it with disease predisposition (p = 0.03). Epistatic interaction analysis by multifactor dimensionality reduction approach revealed redundancy between CTLA-4 and FOXP3 genes in influencing the susceptibility to AITD.The genetic variation in CTLA-4 gene with reference to rs231775 polymorphism contributes to an increased predisposition to HT and GD. Also, in conjunction with FOXP3 gene variants it seems to influence the susceptibility to HT and GD respectively. The significance of these findings in combination with antithyroid antibody screening could plausibly contribute towards meticulous case-finding for effective treatment of HT and GD.