Department of Medical Sciences Experimental and Clinical, University of Udine, Udine, Italy.
Liver Int. 2011 Sep;31(8):1137-43. doi: 10.1111/j.1478-3231.2011.02534.x. Epub 2011 Apr 19.
The PNPLA3 rs738409 C>G polymorphism has been found to be strongly associated with non-alcoholic fatty liver disease and with alcoholic liver disease. Whether the PNPLA3 rs738409 polymorphism could be a risk factor for the development of hepatocellular carcinoma (HCC) in cirrhosis patients is unknown.
This study included 483 (344 males) consecutive Italian patients of Caucasian ethnicity affected by cirrhosis, of whom 279 had undergone transplantation for end-stage liver disease while 204 had been referred to our liver and transplant unit for the diagnosis of cirrhosis. The aetiologies were hepatitis C virus=209, hepatitis B virus=76, alcohol=166, metabolic=32. Ile148Met rs738409 transversion was genotyped using an restriction fragment length polymorphism-based assay.
The genotype frequencies of the rs738409 polymorphism were distributed differently in patients with cirrhosis C/C=168, C/G=220, G/G=95 vs controls C/C=218, C/G=175, G/G=35 (P<0.0001). Among cirrhotics, the G allele was over-represented in alcoholic/metabolic (0.505) vs viral (0.368, P<0.001) liver disease. Patients with cirrhosis complicated by HCC were more likely to be G/G homozygotes (38/141) than the remaining patients (57/342, P<0.02). At multivariate analysis, the PNPLA3 rs738409 polymorphism was confirmed to be an independent predictor of HCC occurrence (odds ratio 1.76, 95% confidence interval 1.06-2.92, P<0.05). HCC rates increased from 13/116 (11.2%; female C/() carriers), to 97/295 (32.9%; male C/() carriers and female G/G homozygotes), to 31/72 (43.1%; male G/G homozygotes) (P<0.0001).
The PNPLA3 rs738409 C>G polymorphism is associated with cirrhosis. In synergy with gender, this polymorphism is a strong predictor of HCC occurrence among patients with cirrhosis.
PNPLA3 rs738409 C>G 多态性与非酒精性脂肪性肝病和酒精性肝病密切相关。PNPLA3 rs738409 多态性是否可作为肝硬化患者发生肝细胞癌（HCC）的危险因素尚不清楚。
本研究纳入了 483 例（男性 344 例）连续的意大利白种人肝硬化患者，其中 279 例因终末期肝病接受了移植，204 例因肝硬化在我院肝移植科就诊。病因包括：丙型肝炎病毒=209 例，乙型肝炎病毒=76 例，酒精性=166 例，代谢性=32 例。采用基于限制性片段长度多态性的检测方法对 Ile148Met rs738409 颠换进行基因分型。
肝硬化患者 rs738409 多态性的基因型频率分布与对照组不同（C/C=168 例，C/G=220 例，G/G=95 例 vs C/C=218 例，C/G=175 例，G/G=35 例；P<0.0001）。在肝硬化患者中，酒精性/代谢性肝病（0.505）G 等位基因的出现频率高于病毒性肝病（0.368，P<0.001）。合并 HCC 的肝硬化患者更可能是 G/G 纯合子（38/141 例），而其余患者（57/342 例，P<0.02）更可能是非 G/G 纯合子。多因素分析证实，PNPLA3 rs738409 多态性是 HCC 发生的独立预测因子（比值比 1.76，95%置信区间 1.06-2.92，P<0.05）。HCC 发生率从女性 C/()携带者的 11.2%（13/116）、男性 C/()携带者和女性 G/G 纯合子的 32.9%（97/295）、男性 G/G 纯合子的 43.1%（31/72）增加（P<0.0001）。
PNPLA3 rs738409 C>G 多态性与肝硬化有关。该多态性与性别协同作用，是肝硬化患者 HCC 发生的强有力预测因子。
