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首页> 外文期刊>Developmental Immunology: Journal of Immunology Research >SNP Analysis of Genes Implicated in T Cell Proliferation in Primary Biliary Cirrhosis
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SNP Analysis of Genes Implicated in T Cell Proliferation in Primary Biliary Cirrhosis

机译：SNP分析与原发性胆汁性肝硬化T细胞增殖相关的基因

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Previous studies on primary biliary cirrhosis (PBC) have focused on the role of T lymphocytes as potential effectors of tissue injury. We hypothesized that single nucleotide polymorphisms (SNPs) of genes involved in lymphocyte proliferation would be responsible for uncontrolled expansion of T cells and autoreactivity. To address this, we genotyped DNA from 154 patients with PBC and 166 ethnically matched healthy controls for SNPs of five candidate genes (60G/A CTLA-4, 1858 C/T LYP, -IVS9 C/T foxp3, p1323 C/G ICOS and -9606 T/C CD25) using a TaqMan assay.We report herein a statistically significant decrease in homozygosity rate for the 60A?CTLA-4 allele in patients with PBC compared to controls (p= 0.0411). Moreover, we found a significant association of the same allele and of the LYP?T allele with anti-mitochondrial antibody (AMA) serum negativity (p= 0.0304 and 0.0094, respectively). No association between any of the other studied SNPs and PBC susceptibility, progression, or AMA status was observed. In conclusion, given the high prevalence of SNPs in CTLA-4 detected in numerous autoimmune diseases, we encourage a more detailed genetic analysis of this candidate gene. Further, although obtained from a limited number of AMA-negative subjects, our data suggest a potential genetic heterogeneity for this specific subgroup of patients with PBC.
机译：先前对原发性胆汁性肝硬化（PBC）的研究集中于T淋巴细胞作为组织损伤的潜在效应子的作用。我们假设参与淋巴细胞增殖的基因的单核苷酸多态性（SNPs）将导致T细胞不受控制的扩增和自身反应性。为了解决这个问题，我们对154个PBC患者和166个种族匹配的健康对照的DNA进行了基因分型，以检测五个候选基因（60G / A CTLA-4、1858 C / T LYP，-IVS9 C / T foxp3，p1323 C / G ICOS使用TaqMan分析法检测到-9606 T / C CD25）。我们在此报告与对照组相比，PBC患者60AΔCTLA-4等位基因纯合率的统计学显着降低（p = 0.0411）。此外，我们发现相同等位基因和LYPΔT等位基因与抗线粒体抗体（AMA）血清阴性之间存在显着关联（分别为p = 0.0304和0.0094）。没有观察到任何其他研究的SNP与PBC敏感性，进展或AMA状态之间的关联。总之，鉴于在许多自身免疫性疾病中检测到的CTLA-4中SNP的高流行，我们鼓励对该候选基因进行更详细的遗传分析。此外，尽管从有限数量的AMA阴性受试者中获得，但我们的数据表明该PBC患者这一特定亚组的潜在遗传异质性。

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