Supplementary Material for: The risk of cirrhosis and its complications based on PNPLA3 rs738409 G allele frequency

Background: Data regarding the influence of patatin-like phospholipase domain-containing 3 (PNPLA3) polymorphism for patients with liver cirrhosis (LC) are scarce. Objective: This study assesses the role of the PNPLA3 polymorphism for the development of LC and its complications by the findings of genetic examinations. Methods: Patients with LC caused by virus (n = 157), alcohol (n = 104), nonalcoholic fatty liver disease (NAFLD) (n = 106), or autoimmune disease (n = 33) and without LC (n = 128) were enrolled. LC were composed of the present and absent of complications, such as variceal bleeding, hepatic ascites, and/or hepatic encephalopathy. To assess the role of the PNPLA3 polymorphism, odds ratio (OR) for the rs738409 variant was calculated for the patients between (i) with LC and without LC in the entire cohort, and (ii) the present and absent of complications in the patients with LC. Results: There was a significant difference among the patients without LC and those with alcohol, NAFLD related LC in the frequency of G alleles (p < 0.001, both). According to complications of LC, the OR for NAFLD related cirrhosis significantly increased in the presence of the two mutated alleles (OR = 3.165; p = 0.046) when the wild type was used as the reference. However, there were no significant risks for the complications in the virus and alcohol related cirrhosis unless there was a presence of G alleles. Conclusion: The PNPLA3 polymorphism was associated with the risk of NAFLD related LC and its complications.

背景：关于肝硬变（LC）患者中 patatin 样磷脂酶结构域含有 3 型（PNPLA3）多态性影响的数据极为匮乏。目标：本研究通过遗传检查的结果，评估 PNPLA3 多态性在 LC 发病及其并发症中的作用。方法：纳入了由病毒（n = 157）、酒精（n = 104）、非酒精性脂肪性肝病（NAFLD）（n = 106）或自身免疫性疾病（n = 33）引起的肝硬变患者以及无肝硬变者（n = 128）。肝硬变患者包括并发症存在与否，如食管静脉曲张出血、腹水以及/或肝性脑病。为了评估 PNPLA3 多态性的作用，计算了全队列中肝硬变患者和无肝硬变患者以及肝硬变患者并发症存在与否的 rs738409 变体的比值比（OR）。结果：在无肝硬变患者与酒精、NAFLD 相关肝硬变患者之间，G 等位基因频率存在显著差异（p < 0.001，两者均为）。根据肝硬变的并发症，当野生型作为参照时，与非 NAFLD 相关的肝硬化相比，存在两个突变等位基因时，NAFLD 相关肝硬化的比值比显著增加（OR = 3.165；p = 0.046）。然而，除非存在 G 等位基因，否则病毒和酒精相关的肝硬化并发症风险并无显著增加。结论：PNPLA3 多态性与 NAFLD 相关肝硬变及其并发症的风险相关。