Patatin-like phospholipase domain-containing 3 (PNPLA3) and transmembrane 6-superfamily member 2 (TM6SF2) polymorphisms have major impact for fibrosis due to steatohepatitis. However, there are scant data about correlations between cirrhosis-related complications and the polymorphisms of these genes. Therefore, we aimed to determine the role of the PNPLA3 and TM6SF2 polymorphisms in fibrosis progression for patients with liver cirrhosis. A multicenter study was performed at six hospitals in Japan enrolling 400 patients with liver cirrhosis caused by virus (n = 157), alcohol (n = 104), nonalcoholic fatty liver disease (NAFLD) (n = 106), or autoimmune disease (n = 33). These cirrhotic patients included those with complications of variceal bleeding, hepatic ascites, and/or hepatic encephalopathy and those without. To assess the role of the PNPLA3 and TM6SF2 polymorphisms in patients with cirrhosis related complications, we calculated the odds ratio and relative risk for the rs738409 and rs58542926 polymorphisms. We also accessed whether or not the interaction between these two polymorphisms contributed to cirrhosis related complications. As a result, the odds ratio for complications in the NAFLD group significantly increased in the presence of the rs738409 GG genotype when the CC genotype was used as the reference. There were no significant risks between complications and the presence of the rs738409 G allele in the virus or alcohol groups. There were no significant risks of complications in the frequency of the rs58542926 T polymorphism regardless of the etiology of liver cirrhosis. The interaction between the trs738409 and rs58542926 polymorphisms had the highest odds ratio of 2.415 for complications in the rs738409 GG + rs58542926 (CT+TT) group when rs738409 (CC+CG) + TM6SF2 CC was used as the reference in the NAFLD group.

中文翻译：

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PNPLA3和TM6SF2在肝硬化相关并发症中的作用

含Patatin样磷脂酶结构域3（PNPLA3）和跨膜6超家族成员2（TM6SF2）多态性对脂肪性肝炎引起的纤维化具有重要影响。但是，关于肝硬化相关并发症与这些基因多态性之间相关性的数据很少。因此，我们旨在确定PNPLA3和TM6SF2多态性在肝硬化患者纤维化进展中的作用。在日本的六家医院进行了一项多中心研究，纳入了400例由病毒（n = 157），酒精（n = 104），非酒精性脂肪肝病（NAFLD）（n = 106）或自身免疫性疾病（n = 33）。这些肝硬化患者包括具有静脉曲张破裂出血，肝腹水和/或肝性脑病并发症的患者，以及没有肝硬化患者。为了评估PNPLA3和TM6SF2多态性在肝硬化相关并发症患者中的作用，我们计算了rs738409和rs58542926多态性的比值比和相对风险。我们还研究了这两个多态性之间的相互作用是否导致了肝硬化相关并发症。结果，当使用CC基因型作为参考时，在存在rs738409 GG基因型的情况下，NAFLD组并发症的优势比显着增加。在病毒或酒精组中，并发症与rs738409 G等位基因的存在之间没有显着风险。不论肝硬化的病因如何，rs58542926 T多态性的发生频率均无并发症的显着风险。