PNPLA3 Gene Polymorphism Is Associated With Predisposition to and Severity of Alcoholic Liver Disease
PNPLA3 Gene Polymorphism Is Associated With Predisposition to and Severity of Alcoholic Liver Disease
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DOI：
10.1038/ajg.2015.137
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发表时间：
2015-06-01
影响因子：
9.8
通讯作者：
Singal, Ashwani K.
中科院分区：
文献类型：
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作者：
Salameh, Habeeb;Raff, Evan;Singal, Ashwani K.
目的：马铃薯糖蛋白样磷脂酶结构域蛋白3（PNPLA 3）基因中148位异亮氨酸-甲硫氨酸取代（rs738409 C>G）的遗传多态性赋予脂肪变性的风险。PNPLA 3基因多态性与酒精性肝病（ALD）相关。我们进行了系统的回顾和荟萃分析，以检查这种遗传多态性与ALD谱及其severity.METHODS：Medline，Embase，和科克伦图书馆的关联PNPLA 3多态性和ALD谱：酒精性脂肪肝（AFL），酒精性肝损伤（ALI），酒精性肝硬化（AC），肝细胞癌（HCC）的研究进行了检索。合并数据报告为比值比（OR）和95%置信区间。使用I2统计量评估异质性，使用Egger检验和Begg和Mazumdar检验评估发表偏倚。结果：在纳入本次汇总分析的10项研究中，与对照组相比，rs738409 CG和GG在ALI患者中的OR分别为1.45（1.24-1.69）和2.22（1.50-3.28），与CC相比。AC组的OR值分别为2.09（1.79-2.44）和3.37（2.49-4.58），AC合并HCC组的OR值分别为2.87（1.61-5.10）和12.41（6.99-22.03）。AFL的数据不一致。在ALD患者中，AC与脂肪肝（FL）患者相比，CG和GG基因型的OR分别为2.62（1.73-3.97）和8.45（2.52-28.37）。AC与ALI的相似OR分别为1.98（1.24-3.17）和3.86（1.18-12.60）。AC患者中CG和GG基因型与HCC发生的OR值分别为1.43（0.76-2.72）和2.81（1.57-5.01）。个体参与者数据分析显示，年龄易患AC在ALI patients.CONCLUSIONS：PNPLA 3基因多态性（rs738409 C>G）与增加的风险，为整个谱ALD饮酒者，包括ALI，AC，和HCC。需要研究来阐明PNPLA 3多态性与酗酒者脂肪变性的关系。PNPLA 3基因可能成为ALD治疗的靶点。
OBJECTIVES: The genetic polymorphism with an isoleucine-to-methionine substitution at position 148 (rs738409 C>G) in the patatin-like phospholipase domain protein 3 (PNPLA3) gene confers risk of steatosis. PNPLA3 polymorphism is shown to be associated with alcoholic liver disease (ALD). We performed a systematic review and meta-analysis to examine association of this genetic polymorphism with ALD spectrum and its severity.METHODS: Medline, Embase, and Cochrane Library were searched for studies on association of PNPLA3 polymorphism and ALD spectrum: alcoholic fatty liver (AFL), alcoholic liver injury (ALI), alcoholic cirrhosis (AC), and hepatocellular carcinoma (HCC). Pooled data are reported as odds ratio (OR) with 95% confidence interval. Heterogeneity was assessed using the I 2 statistics and publication bias using Egger's test and Begg and Mazumdar's test. Individual participant data obtained from five studies were used for subgroup analyses.RESULTS: Among 10 studies included in this pooled analysis, compared with controls, OR for rs738409 CG and GG among ALI patients was 1.45 (1.24-1.69) and 2.22 (1.50-3.28), respectively, compared with CC. Respective OR among AC patients was 2.09 (1.79-2.44) and 3.37 (2.49-4.58) and among AC patients with HCC was 2.87 (1.61-5.10) and 12.41 (6.99-22.03). Data for AFL were inconsistent. Among ALD patients, OR of CG and GG genotypes was 2.62 (1.73-3.97) and 8.45 (2.52-28.37), respectively, for AC compared with fatty liver (FL) patients. Similar OR for AC compared with ALI was 1.98 (1.24-3.17) and 3.86 (1.18-12.60). The OR for CG and GG genotypes among AC patients for HCC occurrence was 1.43 (0.76-2.72) and 2.81 (1.57-5.01), respectively. Individual participant data analysis showed age to predispose to AC among ALI patients.CONCLUSIONS: PNPLA3 genetic polymorphism (rs738409 C>G) is associated with increased risk for the entire spectrum of ALD among drinkers including ALI, AC, and HCC. Studies are needed to clarify association of PNPLA3 polymorphism and steatosis in alcoholics. PNPLA3 gene may potentially be a therapeutic target in ALD.