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首页> 外文期刊>Cellular immunology >A significant association of the CTLA4 gene variants with the risk of autoimmune Graves' disease in ethnic Kashmiri population
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A significant association of the CTLA4 gene variants with the risk of autoimmune Graves' disease in ethnic Kashmiri population

机译：CTLA4基因变异与克什米尔人群自身免疫坟墓疾病风险的重要关联

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摘要

Graves' disease (GD) is the commonest cause of hyperthyroidism in populations with adequate iodine intake. It results from an abnormality in the immune system, which produces unique antibodies causing over production of thyroid hormones and glandular hyperplasia in individuals with genetic susceptibility. The Cytotoxic Lymphocyte Associated Antigen-4 (CTLA4) gene product serves the important function of immunomodulation, thereby helping in maintenance of peripheral self-tolerance. Studies on the association of the CTLA4 SNPs with GD have shown variations in the results from different populations. Since no such study has been carried out in ethnic Kashmiri population, we aimed to study a possible association of the CTLA4 SNPs ( + 49 A/G, - 318C/T, CT 60 A/G and -1661 A/G) with GD. A total of 285 individuals (135 patients with GD and 150 healthy individuals) were genotyped using PCR-RFLP method and the results showed statistically significant differences in genotypic and allelic frequencies of cases and controls for + 49 A/G SNP (p = < 0.001; OR = 5.14; CI = 2.17-12.19) and CT 60 A/G SNP (p = < 0.001; OR = 6.9; CI = 2.8-16.6), while - 318C/T and -1661 A/G SNPs showed no significant association. We also studied the mRNA expression of the CTLA4 in patients with GD and healthy individuals by Real-Time PCR and found a decreased expression of the CTLA4 mRNA in PBMCs of patients with GD as compared to healthy controls with a - 3.71-fold change. We conclude that the CTLA4 + 49 A/G and CT 60 A/G SNPs have a significant association with the risk of GD development in Kashmiri population and CTLA4 mRNA expression is significantly decreased in GD.
机译：Graves'疾病（GD）是具有足够碘摄入量的血红素中最常见的原因。它来自免疫系统中的异常，它产生了具有遗传易感性的个体中甲状腺激素和腺增生的独特抗体。细胞毒性淋巴细胞相关抗原-4（CTLA4）基因产物用于免疫调节的重要功能，从而有助于维持外周自耐受。 CTLA4 SNP与GD的关联的研究显示了不同群体结果的变化。由于没有在克什米尔人口中进行这种研究，我们旨在研究CTLA4 SNPS（+ 49A / g， - 318C / T，CT 60a / g和-1661a / g）的可能缔合。使用PCR-RFLP方法，共有285个个体（135例GD和150名健康个体），结果表明基因型和等位基因频率的统计学显着差异，对照组+ 49A / g SNP（P = <0.001） ;或= 5.14; CI = 2.17-12.19）和CT 60a / g SNP（P = <0.001;或= 6.9; CI = 2.8-16.6），而 - 318C / T和-1661 A / G SNP没有显着协会。我们还通过实时PCR研究了CTLA4对GD和健康个体患者的MRNA表达，并发现与GD患者的PBMC中CTLA4 mRNA的表达减少，与A-3.71倍的健康对照相比。我们得出结论，CTLA4 + 49A / g和CT 60a / g SNP与Kashmiri群体中GD发育的风险有重大关联，CTLA4 mRNA表达在GD中显着降低。

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