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

Abstract

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.

Keywords:

• Non-alcoholic fatty liver disease
• cardiovascular disease
• mortality
• metabolic syndrome
• PNPLA3
• TM6SF2
• MBOAT7

Acknowledgements

The authors thank Markku Päivänsalo, MD, PhD, for excellent liver ultrasound examinations and the laboratory staff and research nurses at the Clinical Research Center, Oulu University Hospital. In particular, Ms. Saija Kortetjärvi is appreciated for the able accomplishment of genotyping. The present study was granted by Jussi Lalli’s and Eva Mariapori-Lalli’s Foundation; the Medical Foundation of Vaasa, Vaasa, Finland; and the State Research Funding of Vaasa Hospital District. All these non-profit organizations are warmly acknowledged.

Disclosure statement

The authors report no conflicts of interest.

Additional information

Funding

This work was supported by the Jussi Lalli’s and Eva Mariapori-Lalli’s Foundation; the Medical Foundation of Vaasa, Vaasa, Finland; and the State Research Funding of Vaasa Hospital District.