Meta-Analysis of the Influence of I148M Variant of Patatin-Like Phospholipase Domain Containing 3 Gene (PNPLA3) on the Susceptibility and Histological Severity of Nonalcoholic Fatty Liver Disease
Meta-Analysis of the Influence of I148M Variant of Patatin-Like Phospholipase Domain Containing 3 Gene (PNPLA3) on the Susceptibility and Histological Severity of Nonalcoholic Fatty Liver Disease
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DOI：
10.1002/hep.24283
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发表时间：
2011-06-01
期刊：
影响因子：
13.5
通讯作者：
Pirola, Carlos J.
中科院分区：
文献类型：
--
作者：
Sookoian, Silvia;Pirola, Carlos J.
我们的目的是评估I148 M（rs738409 C/G）patatin样磷脂酶结构域3（PNPLA 3）变体对不同人群非酒精性脂肪肝（NAFLD）和疾病严重程度的影响强度。我们通过荟萃分析进行了系统评价;文献检索确定了16项研究。我们的结果表明，rs738409不仅对肝脏脂肪积累产生了强烈的影响，（GG纯合子与CC纯合子相比，显示73%的高脂脂肪含量，数据来自2，937名受试者; P <1x10（-9）），也是一种更具侵袭性的疾病的易感性（GG纯合子与CC纯合子相比，坏死性炎症评分升高的风险高3.24倍，发生纤维化的风险高3.2倍; P < 1 × 10 - 9;分别来自1，739和2，251个人的数据）。非酒精性脂肪性肝炎（NASH）在GG纯合子中的发生率高于CC纯合子（比值比[OR] 3.488，95%可信区间[CI] 1.859-6.545，随机模型; P < 2 × 10 - 4;数据来自2,124例患者）。与变异杂合性相关的风险评估表明，加性遗传模型最好地解释了rs738409对发展NAFLD的易感性的影响。然而，携带两个G等位基因似乎不会增加严重组织学特征的风险。荟萃回归分析显示，男性性别与rs738409对肝脏脂肪含量的影响呈负相关（斜率：-22.45 +/- 1.04; P < 0.02）。与CC基因型相比，rs738409 GG基因型与血清丙氨酸氨基转移酶水平升高28%相关。结论：通过总结大量的证据，这项研究提供了明确的证据，证明rs738409是世界各地不同人群中NAFLD自然史的强有力修饰剂。（肝脏学2011;53：1883-1894）
Our objective was to estimate the strength of the effect of the I148M (rs738409 C/G) patatin-like phospholipase domain containing 3 (PNPLA3) variant on nonalcoholic fatty liver (NAFLD) and disease severity across different populations. We performed a systematic review by a meta-analysis; literature searches identified 16 studies. Our results showed that rs738409 exerted a strong influence not only on liver fat accumulation (GG homozygous showed 73% higher lipid fat content when compared with CC ones, data from 2,937 subjects; P < 1 x 10(-9)), but also on the susceptibility of a more aggressive disease (GG homozygous had 3.24-fold greater risk of higher necroinflammatory scores and 3.2-fold greater risk of developing fibrosis when compared with CC homozygous; P < 1 x 10(-9); data from 1,739 and 2,251 individuals, respectively). Nonalcoholic steatohepatitis (NASH) was more frequently observed in GG than CC homozygous (odds ratio [OR] 3.488, 95% confidence interval [CI] 1.859-6.545, random model; P < 2 x 10(-4); data from 2,124 patients). Evaluation of the risk associated with heterozygosity for the variant suggests that the additive genetic model best explains the effect of rs738409 on the susceptibility to develop NAFLD. Nevertheless, carrying two G alleles does not seem to increase the risk of severe histological features. Meta-regression showed a negative correlation between male sex and the effect of rs738409 on liver fat content (slope: -22.45 +/- 1.04; P < 0.02). The rs738409 GG genotype versus the CC genotype was associated with a 28% increase in serum alanine aminotransferase levels. Conclusion: By summarizing the amount of evidence, this study provided unequivocal evidence of rs738409 as a strong modifier of the natural history of NAFLD in different populations around the world. (HEPATOLOGY 2011;53:1883-1894)