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[鸟氨酸脱羧酶抗酶抑制剂1基因多态性与中国乙肝患者肝硬化相关]

[Polymorphism of ornithine decarboxylase antizyme inhibitor 1 gene is associated with liver cirrhosis in Chinese hepatitis B patients].

作者信息

Peng Li-Jun, Guo Jin-Sheng, Zhang Zhe, Shi Hong, Wang Jian, Friedman Scott L, Sninsky John J, Wang Ji-Yao

机构信息

Division of Digestive Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.

出版信息

Zhonghua Gan Zang Bing Za Zhi. 2011 Mar;19(3):169-73. doi: 10.3760/cma.j.issn.1007-3418.2011.03.005.

Abstract

A cirrhosis risk score (CRS) comprised of single nucleotide polymorphisms (SNPs) in seven genes that predicts the risk of cirrhosis in Caucasian hepatitis C has been reported. The present study was to evaluate the association of 11 separate but related SNPs and the CRS with cirrhosis risk in Chinese hepatitis B patients. A total of 563 Chinese subjects with persistent HBV infection (349 with evident liver cirrhosis and 214 without cirrhosis clinically or pathologically) were studied. The candidate SNPs were detected with a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) method. The allele frequency and genotype distribution of each polymorphism as well as the CRS value within the cirrhosis and non-cirrhosis subjects were compared. The rs2679757 polymorphism of the antizyme inhibitor 1 (AZIN1) gene was associated with the risk of cirrhosis (x2 = 6.79, P = 0.03, odds ratio for GG+AG versus AA = 1.63, 95% confidence interval = 1.13-2.35). A gene variant (rs886277) in the transient receptor potential cation channel subfamily M, member 5 gene (TRPM5) was associated with liver cirrhosis, but did not reach statistical significance (x2 = 5.77, P = 0.06). Two SNPs (rs4986791, rs62522600) are not polymorphic in Chinese. Genotype frequencies of other SNPs were not different between the cirrhosis and non-cirrhosis groups. The overall CRS values were not different between the cirrhotic and non-cirrhotic groups (median value 0.57 versus 0.62, Z = -1.05, P = 0.29). SNP rs2679757 in the AZIN1 gene is associated with the risk of HBV-related liver cirrhosis in Chinese. The CRS for Caucasian population has limited applicability for predicting liver cirrhosis in Chinese hepatitis B patients. SNPs associated with cirrhosis prognosis in hepatitis B patients and liver diseases with other etiologies warrant further clinical validation.

摘要

据报道,一种由7个基因中的单核苷酸多态性(SNP)组成的肝硬化风险评分(CRS)可预测白种人丙型肝炎患者的肝硬化风险。本研究旨在评估11个单独但相关的SNP以及CRS与中国乙型肝炎患者肝硬化风险的相关性。共研究了563例持续HBV感染的中国受试者(349例临床或病理诊断为明显肝硬化,214例无肝硬化)。采用基质辅助激光解吸/电离飞行时间质谱(MALDI-TOF MS)方法检测候选SNP。比较了肝硬化组和非肝硬化组中各多态性的等位基因频率、基因型分布以及CRS值。抗酶抑制剂1(AZIN1)基因的rs2679757多态性与肝硬化风险相关(x2 = 6.79,P = 0.03,GG + AG对AA的比值比 = 1.63,95%置信区间 = 1.13 - 2.35)。瞬时受体电位阳离子通道亚家族M成员5基因(TRPM5)中的一个基因变异(rs886277)与肝硬化相关,但未达到统计学显著性(x2 = 5.77,P = 0.06)。两个SNP(rs4986791、rs62522600)在中国人群中无多态性。其他SNP的基因型频率在肝硬化组和非肝硬化组之间无差异。肝硬化组和非肝硬化组的总体CRS值无差异(中位数分别为0.57和0.62,Z = -1.05,P = 0.29)。AZIN1基因中的SNP rs2679757与中国HBV相关肝硬化风险相关。白种人群的CRS在预测中国乙型肝炎患者肝硬化方面适用性有限。与乙型肝炎患者肝硬化预后相关的SNP以及其他病因的肝病值得进一步临床验证。

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