自身免疫性肝炎与白细胞介素-2的单核苷酸多态性相关，但与干扰素-γ无关。

Autoimmune hepatitis association with single nucleotide polymorphism of interleukin-2, but not interferon-gamma.

作者信息

Yousefi Azizollah, Mahmoudi Elham, Baradaran Noveiry Behnoud, Zare Bidoki Alireza, Sadr Maryam, Motamed Farzaneh, Najafi Mehri, Farahmand Fatemeh, Khodadad Ahmad, Fallahi Gholam Hossein, Rezaei Nima

机构信息

Department of Gastroenterology, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.

Molecular Immunology Research Center, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Clin Res Hepatol Gastroenterol. 2018 Apr;42(2):134-138. doi: 10.1016/j.clinre.2017.06.005. Epub 2017 Dec 26.

DOI:10.1016/j.clinre.2017.06.005

PMID:29288086

Abstract

BACKGROUND

Autoimmune hepatitis (AIH) is a chronic inflammation in hepatocellular tissues associated with circulating autoantibodies. Imbalance in T-cells population and dysregulation in several cytokine profiles has been implicated in pathogenesis of AIH. This study was performed to assess potential association of AIH with interleukin-2 (IL-2) and interferon-gamma (IFN-γ) genes single nucleotide polymorphisms (SNPs).

METHODS

Fifty-six patients with AIH and 139 healthy individuals were enrolled in this study. IL-2 and IFN-γ typing was performed, using polymerase chain reaction with sequence-specific primers (PCR-SSP) assay. The frequencies of alleles, genotypes and haplotypes in AIH patients were compared to healthy controls.

RESULTS

IL-2 T allele at position +166 (rs2069763) showed significant higher frequency in AIH group (36%), compared to the controls (21%) (OR=2.06; 95% CI, 1.24-3.43, P-value<0.01). The frequency of IL-2 TT genotype at +166 position was also associated with AIH (OR=18.68, 95% CI 3.74-126.04, P-value<0.01). G/T alleles of IL-2 at -330 (rs2069762) and A/T alleles on UTR +5644 position at IFN-γ and their subsequent haplotypes, did not show significant association with AIH.

CONCLUSIONS

This study identified IL-2T allele at +166 position and TT genotype as susceptibility gene in AIH which would provide better understandings into the mechanisms of AIH and potential immune modulation therapies.

摘要

背景

自身免疫性肝炎（AIH）是一种与循环自身抗体相关的肝细胞组织慢性炎症。T细胞群体失衡和多种细胞因子谱失调与AIH的发病机制有关。本研究旨在评估AIH与白细胞介素-2（IL-2）和干扰素-γ（IFN-γ）基因单核苷酸多态性（SNP）之间的潜在关联。

方法

本研究纳入了56例AIH患者和139名健康个体。采用序列特异性引物聚合酶链反应（PCR-SSP）分析法进行IL-2和IFN-γ分型。将AIH患者的等位基因、基因型和单倍型频率与健康对照进行比较。

结果

与对照组（21%）相比，AIH组中位于+166（rs2069763）位置的IL-2 T等位基因频率显著更高（36%）（比值比=2.06；95%可信区间，1.24-3.43，P值<0.01）。位于+166位置的IL-2 TT基因型频率也与AIH相关（比值比=18.68，95%可信区间3.74-126.04，P值<0.01）。位于-330（rs2069762）位置的IL-2的G/T等位基因以及IFN-γ的UTR +5644位置的A/T等位基因及其随后的单倍型与AIH无显著关联。