慢性乙型肝炎中细胞因子基因多态性与肝纤维化的关联

Association of cytokine gene polymorphisms and liver fibrosis in chronic hepatitis B.

作者信息

Chan Henry L-Y, Tse Ada M-L, Chim Angel M-L, Wong Vincent W-S, Choi Paul C-L, Yu Jun, Zhang Mingdong, Sung Joseph J-Y

机构信息

Institute of Digestive Disease and Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong.

出版信息

J Gastroenterol Hepatol. 2008 May;23(5):783-9. doi: 10.1111/j.1440-1746.2007.05110.x. Epub 2007 Jul 21.

DOI:10.1111/j.1440-1746.2007.05110.x

PMID:17645476

Abstract

BACKGROUND AND AIM

As liver fibrosis is the result of persistent necroinflammation in the liver, pro-inflammatory cytokines secreted in response to cell injury have a central role in the pathogenesis of liver fibrosis. We aimed to investigate the association of cytokine gene polymorphism and liver fibrosis among Chinese patients with chronic hepatitis B.

METHODS

Polymorphisms at interleukin-10 (IL-10-627, -1117), interleukin-1-beta (IL-1beta-511, -31, -3964), interleukin-1 receptor antagonist (IL-1RN), and tumor necrosis factor-alpha (TNF-alpha-308, -238) among Chinese chronic hepatitis B patients were determined. Severe liver fibrosis was defined as Ishak fibrosis score = 4 (of 6).

RESULTS

Fifty-nine of 273 (22%) patients had severe fibrosis. The distribution of genotypes for IL-10-627 was CC (11%), CA (41%), and AA (48%). The CC genotype at IL-10-627 was protective against severe fibrosis (odds ratio (OR) 0.11; 95% CI 0.014-0.82; P = 0.032). After adjusted for baseline variables, the adjusted OR of CC genotypes at IL-10-627 for severe fibrosis was 0.063 (95% CI 0.06-0.64; P = 0.063). Other gene polymorphisms at IL-1beta, IL-1RN, TNF-alpha, and IL-10 had no significant association with severe fibrosis. Weak linkage disequilibrium was observed between IL-10-627 and IL-10-1117 with linkage disequilibrium coefficient of 0.12 (P < 0.001). The distribution of haplotypes of IL-10-1117 and IL-10-627 was A-A (69%), A-C (26%), and G-C (5%). High and intermediate IL-10 production (A-C and G-C) haplotypes were protective against severe fibrosis (OR 0.62; 95% CI 0.39-0.99; P = 0.046).

CONCLUSIONS

High production genotype and haplotypes of IL-10 were associated with less severe liver fibrosis in chronic hepatitis B in Chinese.

摘要

背景与目的

由于肝纤维化是肝脏持续性坏死性炎症的结果，细胞损伤时分泌的促炎细胞因子在肝纤维化发病机制中起核心作用。我们旨在研究中国慢性乙型肝炎患者细胞因子基因多态性与肝纤维化的关系。

方法

测定中国慢性乙型肝炎患者白细胞介素-10（IL-10 -627、-1117）、白细胞介素-1β（IL-1β -511、-31、-3964）、白细胞介素-1受体拮抗剂（IL-1RN）和肿瘤坏死因子-α（TNF-α -308、-238）的多态性。严重肝纤维化定义为Ishak纤维化评分 = 4（满分6分）。

结果

273例患者中有59例（22%）存在严重纤维化。IL-10 -627基因型分布为CC（11%）、CA（41%）和AA（48%）。IL-10 -627的CC基因型对严重纤维化具有保护作用（优势比（OR）0.11；95%可信区间0.014 - 0.82；P = 0.032）。校正基线变量后，IL-10 -627的CC基因型对严重纤维化的校正OR为0.063（95%可信区间0.06 - 0.64；P = 0.063）。IL-1β、IL-1RN、TNF-α和IL-10的其他基因多态性与严重纤维化无显著关联。观察到IL-10 -627与IL-10 -1117之间存在弱连锁不平衡，连锁不平衡系数为0.12（P < 0.001）。IL-10 -1117和IL-10 -627单倍型分布为A - A（69%）、A - C（26%）和G - C（5%）。高和中等IL-10产生（A - C和G - C）单倍型对严重纤维化具有保护作用（OR 0.62；95%可信区间0.39 - 0.99；P = 0.046）。