Impact of patatin‐like phospholipase‐3 (rs738409 C>G) polymorphism on fibrosis progression and steatosis in chronic hepatitis C
Impact of patatin‐like phospholipase‐3 (rs738409 C>G) polymorphism on fibrosis progression and steatosis in chronic hepatitis C
复制标题
patatin样磷脂酶3 (rs738409 C>G)多态性对慢性丙型肝炎纤维化进展和脂肪变性的影响
作者：
E. Trépo;P. Pradat;A. Potthoff;Y. Momozawa;E. Quertinmont;T. Gustot;A. Lemmers;P. Berthillon;L. Amininejad;M. Chevallier;J. Schlué;H. Kreipe;J. Devière;M. Manns;C. Trépo;J. Sninsky;H. Wedemeyer;D. Franchimont;Christophe Moreno
只有 20% 的慢性丙型肝炎 (CHC) 患者会发展为肝硬化，且纤维化进展仍然高度不可预测。最近的一项全基因组关联研究发现了与脂肪变性相关的 patatin 样磷脂酶 3 (PNPLA3) 基因 (rs738409 C>G) 中的遗传变异，该变异被进一步证明会影响非酒精性脂肪肝疾病纤维化的严重程度。本研究的目的是评估这种多态性对 CHC 患者的组织学肝损伤和抗病毒治疗反应的影响。我们从三个欧洲中心（比利时布鲁塞尔 [n = 229]；德国汉诺威 [n = 171]；法国里昂 [n = 137]）招募了 537 名白人 CHC 患者。对这些患者进行了 PNPLA3 (rs738409 C>G) 多态性集中基因分型。我们以横断面和纵向的方式研究了 rs738409 和 PNPLA3 区域中的其他变异对脂肪变性和纤维化的影响。之前与纤维化进展相关的其他七种变异也被包括在内。最后，我们使用干扰素 lambda 3 (IL28B) [rs12979860 C>T] 变体作为比较器和阳性对照，探讨了 rs738409 对标准抗病毒治疗反应的影响。调整年龄、性别、体重指数、饮酒量和糖尿病后，rs738409突变G等位基因纯合子携带者仍面临较高的脂肪变性风险（比值比[OR] 2.55，95%置信区间[CI] 1.08-6.03，P = 0.034）、纤维化（OR 3.13，95% CI 1.50-6.51，P = 0.002）和纤维化进展（OR 2.64，95% CI 1.22-5.67，P = 0.013）。相反，rs738409 与治疗失败并不独立相关（OR 1.07，95% CI 0.46-2.49，P = 0.875），并且不影响临床或生物学变量。结论：PNPLA3 (rs738409 C>G) 多态性有利于 CHC 的脂肪变性和纤维化进展。这种多态性可能代表一种有价值的遗传预测因子和 CHC 肝损伤的潜在治疗靶点。 （肝病学 2011；）
Only 20% of patients with chronic hepatitis C (CHC) will develop cirrhosis, and fibrosis progression remains highly unpredictable. A recent genome‐wide association study identified a genetic variant in the patatin‐like phospholipase‐3 (PNPLA3) gene (rs738409 C>G) associated with steatosis that was further demonstrated to influence severity of fibrosis in nonalcoholic fatty liver disease. The aim of this study was to assess the impact of this polymorphism on histological liver damage and response to antiviral therapy in CHC. We recruited 537 Caucasian CHC patients from three European centers (Brussels, Belgium [n = 229]; Hannover, Germany [n = 171]; Lyon, France [n = 137]); these patients were centrally genotyped for the PNPLA3 (rs738409 C>G) polymorphism. We studied the influence of rs738409 and other variants in the PNPLA3 region on steatosis and fibrosis assessed both in a cross‐sectional and longitudinal manner. Seven other variants previously associated with fibrosis progression were included. Finally, we explored the impact of rs738409 on response to standard antiviral therapy using the interferon lambda 3 (IL28B) [rs12979860 C>T] variant both as a comparator and as a positive control. After adjustment for age, sex, body mass index, alcohol consumption, and diabetes, rs738409 mutant G allele homozygote carriers remained at higher risk for steatosis (odds ratio [OR] 2.55, 95% confidence interval [CI] 1.08‐6.03, P = 0.034), fibrosis (OR 3.13, 95% CI 1.50‐6.51, P = 0.002), and fibrosis progression (OR 2.64, 95% CI 1.22‐5.67, P = 0.013). Conversely, rs738409 was not independently associated with treatment failure (OR 1.07, 95% CI 0.46‐2.49, P = 0.875) and did not influence clinical or biological variables. Conclusion: The PNPLA3 (rs738409 C>G) polymorphism favors steatosis and fibrosis progression in CHC. This polymorphism may represent a valuable genetic predictor and a potential therapeutic target in CHC liver damage. (HEPATOLOGY 2011;)
影响因子：
11.2
作者：
Vaissiere, Thomas;Hung, Rayjean J.;Zaridze, David;Moukeria, Anush;Cuenin, Cyrille;Fasolo, Virgrinie;Ferro, Gilles;Paliwal, Anuparn;Hainaut, Pierre;Brennan, Paul;Tost, Joerg;Boffetta, Paolo;Herceg, Zdenko
通讯作者：
Herceg, Zdenko
影响因子：
29.4
作者：
Leandro, Gioacchino;Mangia, Alessandra;Negro, Francesco
通讯作者：
Negro, Francesco