Department of Endocrinology, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Jammu & Kashmir, India.
Immunology and Molecular Medicine, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Jammu & Kashmir, India.
Gene. 2018 Sep 25;672:88-92. doi: 10.1016/j.gene.2018.06.023. Epub 2018 Jun 9.
Graves' disease is a multifactorial autoimmune disorder of the thyroid gland, with some extra-thyroidal complications like eye and skin abnormalities in some patients. GD is more prevalent in women than men and is the leading cause of hyperthyroidism worldwide. A complex interaction between genetic and environmental factors is the proposed cause which triggers immune system to produce autoantibodies stimulating the TSH receptor, leading to clinical manifestations such as hyperthyroidism, diffuse thyroid enlargement (goiter) and often ophthalmopathy in affected individuals. Various Single nucleotide gene polymorphisms (SNPs) have been associated with the risk of GD development including promoter SNPs in Forkhead Box P3 (FOXP3). FOXP3 is an important regulatory factor for T cell development and differentiation and therefore has a prominent role in suppression of autoimmune reactions which may lead to predisposition of GD. There have been some studies on the association of FOXP3 SNPs with GD, but no such investigation has been carried out in ethnic Kashmiri population. So, we aimed to study a possible association of FOXP3 promoter SNPs (-3279C/A, -2383C/T & -3499 A/G) with GD. Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) was used to genotype 285 individuals (135 GD cases and 150 healthy controls) and the results showed statistically significant differences in genotypic and allelic frequencies of cases and controls for -3279C/A SNP [OR, 3.48; 95% CI (2.05-5.92); P < 0.001] and -2383C/T SNP [OR, 5.62; 95% CI (2.43-13.00); P < 0.001], while no significant association was seen in case of -3499 A/G SNP. We conclude that -3279C/A and -2383C/T SNPs have a highly significant association with the risk of GD development in Kashmiri population.
格雷夫斯病是一种多因素自身免疫性甲状腺疾病，一些患者会出现甲状腺外并发症，如眼部和皮肤异常。GD 在女性中的发病率高于男性，是全球导致甲状腺功能亢进的主要原因。遗传和环境因素的复杂相互作用被认为是触发免疫系统产生刺激 TSH 受体的自身抗体的原因，导致受影响个体出现甲状腺功能亢进、弥漫性甲状腺肿大（甲状腺肿）和眼部病变等临床表现。许多单核苷酸基因多态性（SNP）与 GD 发病风险相关，包括叉头框 P3（FOXP3）启动子 SNP。FOXP3 是 T 细胞发育和分化的重要调节因子，因此在抑制自身免疫反应方面发挥着重要作用，这可能导致 GD 的易感性。已经有一些关于 FOXP3 SNP 与 GD 之间关联的研究，但在克什米尔族群中尚未进行此类研究。因此，我们旨在研究 FOXP3 启动子 SNP（-3279C/A、-2383C/T 和-3499A/G）与 GD 之间的可能关联。聚合酶链反应-限制性片段长度多态性（PCR-RFLP）用于对 285 名个体（135 名 GD 病例和 150 名健康对照者）进行基因分型，结果显示病例和对照组在 -3279C/A SNP 的基因型和等位基因频率方面存在统计学显著差异[OR，3.48；95%CI（2.05-5.92）；P<0.001]和-2383C/T SNP [OR，5.62；95%CI（2.43-13.00）；P<0.001]，而-3499A/G SNP 则无显著相关性。我们得出结论，-3279C/A 和-2383C/T SNP 与克什米尔人群 GD 发病风险高度相关。
