Burza Maria Antonella, Molinaro Antonio, Attilia Maria Luisa, Rotondo Claudia, Attilia Fabio, Ceccanti Mauro, Ferri Flaminia, Maldarelli Federica, Maffongelli Angela, De Santis Adriano, Attili Adolfo Francesco, Romeo Stefano, Ginanni Corradini Stefano
Institute of Medicine, Department of Molecular and Clinical Medicine, Wallenberg Laboratory, University of Gothenburg, Gothenburg, Sweden.
Liver Int. 2014 Apr;34(4):514-20. doi: 10.1111/liv.12310. Epub 2013 Sep 19.
BACKGROUND & AIMS: Environmental and genetic factors contribute to alcoholic cirrhosis onset. In particular, age at exposure to liver stressors has been shown to be important in progression to fibrosis in hepatitis C individuals. However, no definite data on the role of age at onset of at-risk alcohol consumption are available. Moreover, patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148M (rs738409) variant has been associated with alcoholic cirrhosis, but only in cross-sectional studies. The aim of this study was to investigate the role of age at onset of at-risk alcohol consumption and PNPLA3 I148M variant on alcoholic cirrhosis incidence.
A total of 384 at-risk alcohol drinkers were retrospectively examined. The association among age at onset of at-risk alcohol consumption, PNPLA3 I148M variant and cirrhosis incidence was tested.
A higher incidence of alcoholic cirrhosis was observed in individuals with an older (≥24 years) compared with a younger (<24) age at onset of at-risk alcohol consumption (P-value < 0.001). Moreover, PNPLA3 148M allele carriers showed an increased incidence of cirrhosis (P-value < 0.001). Both age at onset of at-risk alcohol consumption and PNPLA3 148M allele were independent risk factors for developing cirrhosis (H.R. (95% C.I.): 2.76 (2.18-3.50), P-value < 0.001; 1.53(1.07-2.19), P-value = 0.021 respectively). The 148M allele was associated with a two-fold increased risk of cirrhosis in individuals with a younger compared with an older age at onset of at-risk alcohol consumption (H.R. (95% C.I.): 3.03(1.53-6.00) vs. 1.61(1.09-2.38).
Age at onset of at-risk alcohol consumption and PNPLA3 I148M genetic variant are independently associated with alcoholic cirrhosis incidence.
环境和遗传因素促使酒精性肝硬化发病。尤其是，丙型肝炎患者接触肝脏应激源时的年龄在纤维化进展过程中已被证明很重要。然而，关于有风险饮酒起始年龄的作用尚无确切数据。此外，含帕他汀样磷脂酶结构域蛋白3（PNPLA3）I148M（rs738409）变异与酒精性肝硬化相关，但仅在横断面研究中。本研究旨在探讨有风险饮酒起始年龄和PNPLA3 I148M变异对酒精性肝硬化发病率的作用。
对384名有风险饮酒者进行回顾性检查。检测有风险饮酒起始年龄、PNPLA3 I148M变异与肝硬化发病率之间的关联。
与有风险饮酒起始年龄较小（<24岁）的个体相比，年龄较大（≥24岁）的个体酒精性肝硬化发病率更高（P值<0.001）。此外，PNPLA3 148M等位基因携带者肝硬化发病率增加（P值<0.001）。有风险饮酒起始年龄和PNPLA3 148M等位基因均为发生肝硬化的独立危险因素（风险比（95%置信区间）：分别为2.76（2.18 - 3.50），P值<0.001；1.53（1.07 - 2.19），P值 = 0.021）。与有风险饮酒起始年龄较大的个体相比，148M等位基因与有风险饮酒起始年龄较小的个体患肝硬化风险增加两倍相关（风险比（95%置信区间）：3.03（1.53 - 6.00）对1.61（1.09 - 2.38））。
有风险饮酒起始年龄和PNPLA3 I148M基因变异与酒精性肝硬化发病率独立相关。
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