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HLA-DQ和IFNL4基因多态性与乙型肝炎病毒感染易感性及清除的关联

Association of HLA-DQ and IFNL4 polymorphisms with susceptibility to hepatitis B virus infection and clearance.

作者信息

Fan Jia-Hao, Hou Si-Hui, Qing-Ling Li, Hu Jun, Peng Hong, Guo Jin-Jun

机构信息

Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Institute of Life Sciences, Chongqing Medical University, Chongqing, China.

出版信息

Ann Hepatol. 2016 Jul-Aug;15(4):532-9.

Abstract

UNLABELLED

Background and aim. Leukocyte antigen DQ (HLA-DQ) and interferon-λ4 (IFNL4) gene polymorphisms were associated with susceptibility to chronic hepatitis B and C virus infection. This study further confirmed that variants of these genes were associated with susceptibility and spontaneous clearance of HBV infection in a Chinese population.

MATERIAL AND METHODS

A total of 1,069 subjects were recruited and divided into three groups i.e. 397 with CLD (HBV-related chronic liver disease), 434 with SC (spontaneous clearance), and 238 HC (healthy controls). HLA-DQrs9275319 and IFNL4rs368234815, rs12971396, rs12979860, and rs8099917SNPs were genotyped using the Sequenom MassARRAY MALDI-TOF system.

RESULTS

HLA-DQ rs9275319 showed a significant association with HBV infection (allele model, OR, 0.514; 95% CI, 0.359-0.738, adjusted p = 0.0003) and with natural clearance (allele model, OR, 1.659; 95% CI, 1.197-2.300, adjusted. However, there was no association between IFNL4 polymorphism and HBV susceptibility or natural clearance (all p > 0.05). The multifactor dimensionality reduction (MDR) test with permutation correction showed that a three-way interaction between IFNL4 and HLA-DQ SNPs was identified for HBV susceptibility (permutation p = 0.009 for the best factor model) and clearance (permutation p = 0.014 for the best factor model).

CONCLUSIONS

The data from the current study provided additional evidence for an SNP-SNP interaction between HLA-DQ and IFNL4 in regulation to HBV infection and natural clearance.

摘要

未标注

背景与目的。白细胞抗原DQ(HLA - DQ)和干扰素λ4(IFNL4)基因多态性与慢性乙型和丙型肝炎病毒感染的易感性相关。本研究进一步证实这些基因的变异与中国人群中HBV感染的易感性和自发清除相关。

材料与方法

共招募1069名受试者,分为三组,即397例慢性肝病患者(HBV相关慢性肝病)、434例自发清除者(SC)和238例健康对照(HC)。使用Sequenom MassARRAY MALDI - TOF系统对HLA - DQ rs9275319以及IFNL4 rs368234815、rs12971396、rs12979860和rs8099917单核苷酸多态性(SNP)进行基因分型。

结果

HLA - DQ rs9275319与HBV感染显著相关(等位基因模型,比值比[OR]为0.514;95%置信区间[CI]为0.359 - 0.738,校正p = 0.0003),与自然清除也显著相关(等位基因模型,OR为1.659;95% CI为1.197 - 2.300,校正后)。然而,IFNL4多态性与HBV易感性或自然清除之间无关联(所有p > 0.05)。经置换校正的多因素降维(MDR)检验表明,IFNL4与HLA - DQ SNP之间的三向相互作用与HBV易感性(最佳因子模型的置换p = 0.009)和清除(最佳因子模型的置换p = 0.014)相关。

结论

本研究数据为HLA - DQ和IFNL4之间在调节HBV感染和自然清除方面的单核苷酸多态性 - 单核苷酸多态性相互作用提供了更多证据。

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