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白细胞介素28受体A基因多态性(rs10903035)与HIV/HCV合并感染患者的胰岛素抵抗有关。

IL28RA polymorphism (rs10903035) is associated with insulin resistance in HIV/HCV-coinfected patients.

作者信息

Jiménez-Sousa M A, Berenguer J, Fernández-Rodríguez A, Micheloud D, Guzmán-Fulgencio M, Miralles P, Pineda-Tenor D, García-Álvarez M, López J C, Aldámiz-Echevarria T, Carrero A, Resino S

机构信息

Unit of Viral Infection and Immunity, National Centre of Microbiology, Instituto de Salud Carlos III, Majadahonda, Spain.

出版信息

J Viral Hepat. 2014 Mar;21(3):189-97. doi: 10.1111/jvh.12130. Epub 2013 Jul 17.

DOI:10.1111/jvh.12130
PMID:24438680
Abstract

Hepatitis C virus (HCV) infection is associated with insulin resistance (IR), although mechanisms leading to IR in these patients are not completely understood. The aim of this study was to evaluate the association of interleukin 28B (IL28B) and interleukin 28 receptor alpha (IL28RA) polymorphisms with IR among human immunodeficiency virus (HIV)/HCV-coinfected patients. We carried out a cross-sectional study on 203 patients. IL28B (rs8099917) and IL28RA (rs10903035) polymorphisms were genotyped by GoldenGate(®) assay. IR was defined as homeostatic model assessment (HOMA) values ≥3.00. Univariate and multivariate generalized linear models (GLM) were used to compare HOMA values and the percentage of patients with IR according to IL28B and IL28RA genotypes. In total, 32% (n = 65/203) of the patients had IR. IL28B rs8099917 TT was not significantly associated with HOMA values and IR. In contrast, rs10903035 AA was significantly associated with high HOMA values taking into account all patients (P = 0.024), as well as the subgroups of patients with significant fibrosis (P = 0.047) and infected with HCV genotype 3 (P = 0.024). Additionally, rs10903035 AA was significantly associated with IR (HOMA ≥3.00) in all patients (adjusted odds ratio (aOR) = 2.02; P = 0.034), in patients with significant fibrosis (aOR = 2.86; P = 0.039) and HCV genotype 3 patients (aOR = 4.89; P = 0.031). In conclusions, IL28RA polymorphism (rs10903035) seems to be implicated in the glucose homeostasis because AA genotype increases the likelihood of IR, but this association was different depending on hepatic fibrosis and HCV genotype.

摘要

丙型肝炎病毒(HCV)感染与胰岛素抵抗(IR)相关,尽管导致这些患者发生IR的机制尚未完全明确。本研究旨在评估白细胞介素28B(IL28B)和白细胞介素28受体α(IL28RA)基因多态性与人类免疫缺陷病毒(HIV)/HCV合并感染患者IR之间的关联。我们对203例患者进行了一项横断面研究。采用金标准(®)检测法对IL28B(rs8099917)和IL28RA(rs10903035)基因多态性进行基因分型。IR定义为稳态模型评估(HOMA)值≥3.00。采用单因素和多因素广义线性模型(GLM),根据IL28B和IL28RA基因型比较HOMA值以及IR患者的百分比。总共有32%(n = 65/203)的患者存在IR。IL28B rs8099917 TT与HOMA值及IR无显著关联。相比之下,考虑所有患者时,rs10903035 AA与高HOMA值显著相关(P = 0.024),在有显著肝纤维化的患者亚组中(P = 0.047)以及感染HCV基因3型的患者中(P = 0.024)也是如此。此外,rs10903035 AA在所有患者中(校正比值比(aOR)= 2.02;P = 0.034)、有显著肝纤维化的患者中(aOR = 2.86;P = 0.039)以及HCV基因3型患者中(aOR = 4.89;P = 0.031)与IR(HOMA≥3.00)显著相关。总之,IL28RA基因多态性(rs10903035)似乎与葡萄糖稳态有关,因为AA基因型增加了IR的可能性,但这种关联因肝纤维化和HCV基因型而异。

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