{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T19:50:56Z","timestamp":1792439456349,"version":"4.5.0"},"reference-count":49,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,1,12]],"date-time":"2022-01-12T00:00:00Z","timestamp":1641945600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31821002"],"award-info":[{"award-number":["31821002"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81873660"],"award-info":[{"award-number":["81873660"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The PNPLA3 and TM6SF2 gene variants have been found to cause NAFLD with a favourable cardiovascular risk profile.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>To investigate the effects of the NAFLD risk alleles on the all\u2010cause and cause\u2010specific mortality in 5581 Chinese adults.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The genome\u2010wide genotypes were detected using a genotyping array and serum lipoprotein profiles were examined using 1H NMR platform. Liver fat content (LFC) was measured using a quantitative ultrasound method. The vital status was determined using official registration data.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Genome\u2010wide association analysis showed that a series of variants in PNPLA3 were associated with LFC, including rs738409 C&gt;G variant (<jats:italic>P<\/jats:italic>\u00a0=\u00a08.6\u00a0\u00d7\u00a010<jats:sup>\u22127<\/jats:sup>). Further analyses validated the associations of TM6SF2 rs58542926 C&gt;T and MBOAT7 rs641738 C&gt;T variants with NAFLD. During 29\u00a0425.1 person\u2010years of follow\u2010up, the overall mortality was 816 per 100\u00a0000 person\u2010years, where 299 deaths were attributable to cardiovascular disease and 85 to liver disease. The PNPLA3 rs738409 C&gt;G variant was independently associated with increased liver\u2010specific mortality (<jats:italic>P<\/jats:italic> for trend\u00a0=\u00a00.034) but reduced cardiovascular mortality (<jats:italic>P<\/jats:italic> for trend\u00a0=\u00a00.047). A composite genetic\u2010predisposition score of PNPLA3, TM6SF2, and MBOAT7 risk alleles presented similar opposite effects on liver\u2010specific and cardiovascular mortality. Moreover, interactions of the NAFLD risk alleles with adiposity for liver\u2010specific mortality were found (<jats:italic>P<\/jats:italic><jats:sub>interaction<\/jats:sub>\u00a0&lt;\u00a00.05). The reduced serum VLDL1 concentration was responsible for the increased liver\u2010specific mortality related to NAFLD risk alleles.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The PNPLA3 rs738409 C&gt;G variant and its combination with TM6SF2 rs58542926 C&gt;T and MBOAT7 rs641738 C&gt;T variants increase liver\u2010specific mortality but reduce cardiovascular mortality in overweight\/obese Chinese.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apt.16772","type":"journal-article","created":{"date-parts":[[2022,1,13]],"date-time":"2022-01-13T03:44:27Z","timestamp":1642045467000},"page":"705-721","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["NAFLD\u2010related gene polymorphisms and all\u2010cause and cause\u2010specific mortality in an Asian population: the Shanghai Changfeng 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