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北印度成年人自身免疫性肝炎患者的 HLA 和非 HLA 基因多态性。

HLA and Non-HLA gene polymorphisms in autoimmune hepatitis patients of North Indian adults.

机构信息

Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Department of Immunopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

出版信息

Front Immunol. 2023 Jan 18;13:984083. doi: 10.3389/fimmu.2022.984083. eCollection 2022.

Abstract

Autoimmune hepatitis (AIH) is a chronic and progressive disease of the liver. This is a multifactorial autoimmune disease with both environmental factors and genetic factors playing a role in its pathogenesis. Certain environmental agents like viruses, drugs, etc., can trigger the disease in a genetically susceptible individual. The present study was aimed to explore the distribution of human leukocyte antigen (HLA)-DRB1, Protein tyrosine phosphatase non-receptor type 22 (PTPN22) and Cytotoxic T-Lymphocyte-associated protein 4 (CTLA-4) polymorphisms in North Indian adult AIH patients and their associations with clinical and pathological characteristics associated with the disease. A total of 147 subjects with 47 cases and 100 healthy controls were enrolled. Diagnosis of AIH was made by Revised International Autoimmune Hepatitis Group scoring system. HLA-DRB1 Typing was done by Luminex-based reverse Sequence-Specific Oligonucleotide Probing (SSOP). Single nucleotide variant (SNV) genotyping for CTLA-4 and PTPN22 was done by simple probe-based SNP arrays. Results indicated SLA positive AIH patients are poor responders to therapy. A significant predispositional association of HLA-DRB1*03 was observed in AIH patients from the North Indian population (p= 0.0001, OR=4.83 (2.30-10.15). The frequency of the GG genotype of CTLA-4 CT 60 was significantly increased in AIH patients compared to controls. Multinomial analysis showed that CTLA-4 CT 60 is an independent predictor for cases.

摘要

自身免疫性肝炎(AIH)是一种慢性进行性肝脏疾病。这是一种多因素自身免疫性疾病,环境因素和遗传因素在其发病机制中都起着作用。某些环境因子,如病毒、药物等,可在遗传易感个体中引发该病。本研究旨在探讨人类白细胞抗原(HLA)-DRB1、蛋白酪氨酸磷酸酶非受体型 22(PTPN22)和细胞毒性 T 淋巴细胞相关蛋白 4(CTLA-4)多态性在北印度成年 AIH 患者中的分布及其与与疾病相关的临床和病理特征的关联。共纳入 147 例受试者,其中 47 例为 AIH 患者,100 例为健康对照。采用修订后的国际自身免疫性肝炎组评分系统诊断 AIH。采用基于 Luminex 的反向序列特异性寡核苷酸探针(SSOP)进行 HLA-DRB1 分型。采用简单探针 SNP 阵列对 CTLA-4 和 PTPN22 的单核苷酸变异(SNV)进行基因分型。结果表明,SLA 阳性的 AIH 患者对治疗反应不佳。在北印度人群中,AIH 患者 HLA-DRB1*03 存在显著的易感性关联(p=0.0001,OR=4.83(2.30-10.15)。与对照组相比,AIH 患者 CTLA-4 CT 60 的 GG 基因型频率显著升高。多项分析表明,CTLA-4 CT 60 是病例的独立预测因子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/754a/9891307/cba856d155f5/fimmu-13-984083-g001.jpg

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