Metabolic syndrome but not genetic polymorphisms known to induce NAFLD predicts increased total mortality in subjects with NAFLD (OPERA study)

Metabolic syndrome (MetS) and genetic polymorphisms PNPLA3 rs738409, TM6SF2 rs58542926 and MBOAT7 rs641738 are known inductors of non-alcoholic fatty liver disease (NAFLD). However, knowledge about how these affect the mortality of subjects with NAFLD is scarce. Therefore, we investigated the impact of MetS, PNPLA3 rs738409, TM6SF2 rs58542926 and MBOAT7 rs641738 on overall and cardiovascular disease (CVD) specific mortality among subjects with or without NAFLD. NAFLD diagnosis was based on liver ultrasound at the baseline. After this and other comprehensive examinations, 958 middle-aged Finns, 249 with NAFLD, were followed for 21 years. The mortality data was gathered from the National Death Registry. After multiple adjustments, the NAFLD individuals with MetS had increased risk of overall mortality as compared to the NAFLD subjects without MetS [2.054 (1.011–4.173, p = .046)]. However, PNPLA3 rs738409 [1.049 (0.650–1.692, p = .844)], TM6SF2 rs58542926 [0.721 (0.369–1.411, p = .340)] or MBOAT7 rs641738 [0.885 (0.543–1.439, p = .621)] did not affect the overall mortality. MetS was also a marker of increased risk of CVD mortality (15% vs. 2%, p = .013) while genetic polymorphisms did not affect CVD mortality. In conclusion, MetS, but not the gene polymorphisms studied, predicts increased overall and CVD-specific mortality among NAFLD subjects.

代谢综合征（MetS）以及PNPLA3 rs738409、TM6SF2 rs58542926、MBOAT7 rs641738这三种基因多态性，是已知的非酒精性脂肪性肝病（NAFLD）诱发因素。然而，目前关于上述因素如何影响非酒精性脂肪性肝病患者死亡率的研究尚少。为此，本研究探讨了代谢综合征、PNPLA3 rs738409、TM6SF2 rs58542926以及MBOAT7 rs641738，对合并与未合并非酒精性脂肪性肝病人群的全因死亡率及心血管疾病（CVD）特异性死亡率的影响。非酒精性脂肪性肝病的诊断以基线肝脏超声检查结果为依据。在完成此项检查及其他全面体检后，研究共纳入958名中年芬兰受试者，其中249名确诊非酒精性脂肪性肝病，随访时长达21年。死亡率数据来源于国家死亡登记库。经多重校正后，相较于无代谢综合征的非酒精性脂肪性肝病患者，合并代谢综合征的非酒精性脂肪性肝病患者全因死亡风险显著升高[2.054 (1.011–4.173, p = .046)]。但PNPLA3 rs738409 [1.049 (0.650–1.692, p = .844)]、TM6SF2 rs58542926 [0.721 (0.369–1.411, p = .340)] 及MBOAT7 rs641738 [0.885 (0.543–1.439, p = .621)] 均未对全因死亡率产生显著影响。代谢综合征同样是心血管疾病死亡率升高的危险因素（15% vs. 2%, p = .013），而上述基因多态性并未对心血管疾病死亡率产生影响。综上，代谢综合征而非本研究涉及的基因多态性，可预测非酒精性脂肪性肝病患者的全因死亡率及心血管疾病特异性死亡率升高。