{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T16:54:09Z","timestamp":1758992049061,"version":"3.41.2"},"reference-count":48,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T00:00:00Z","timestamp":1681689600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Clin Investigation"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p><jats:italic>MBOAT7<\/jats:italic> rs641738 variant is a risk factor for nonalcoholic fatty liver disease (NAFLD) and liver fibrosis, but the relationship between this polymorphism and early liver dysfunction remains uncertain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Eighty outpatients underwent blood analyses, liver imaging by ultrasound and acoustic radiation force impulse shear wave elastography and were genotyped for <jats:italic>MBOAT7<\/jats:italic> (wild\u2010type [WT], rs641738 heterozygous or homozygous) polymorphism using TaqMan assays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>NAFLD was confirmed in 53 patients. Portal uptake and hepatocyte microsomal metabolization of (<jats:sup>13<\/jats:sup>C)\u2010methacetin were explored by measuring <jats:sup>13<\/jats:sup>CO<jats:sub>2<\/jats:sub> appearance in exhaled air. The distribution of the <jats:italic>MBOAT7<\/jats:italic> genotypes was comparable in subjects with or without NAFLD. The majority of subjects with or without NAFLD had fibrosis \u2264 F1 but decreased portal extraction of (<jats:sup>13<\/jats:sup>C)\u2010methacetin, i.e. 78.6% in homozygous, 45.0% in heterozygous and 46.2% in WT for the <jats:italic>MBOAT7<\/jats:italic> variant. Both substrate extraction and microsomal metabolization were mostly defective in the homozygous carriers. The extraction efficiency from portal blood flow was minimal in subjects with both homozygous rs641738 polymorphism and NAFLD, as compared to those with WT\/heterozygous polymorphism, with or without NAFLD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The homozygous <jats:italic>MBOAT7<\/jats:italic> rs641738 polymorphism per se is associated with a reduced extraction efficiency of (<jats:sup>13<\/jats:sup>C)\u2010methacetin from the portal flow pointing to subclinical liver dysfunction independently from liver fibrosis. Liver steatosis worsens (<jats:sup>13<\/jats:sup>C)\u2010methacetin extraction efficiency. We urge to better explore the mechanisms of interaction between external factors and multiple gene polymorphisms (including <jats:italic>MBOAT7<\/jats:italic>), paving the road to primary prevention and novel therapeutic strategies.<\/jats:p><\/jats:sec>","DOI":"10.1111\/eci.14003","type":"journal-article","created":{"date-parts":[[2023,4,8]],"date-time":"2023-04-08T13:02:55Z","timestamp":1680958975000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Effects of <scp><i>MBOAT7<\/i><\/scp> polymorphism and steatosis on liver function assessed by methacetin breath test"],"prefix":"10.1111","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5476-7376","authenticated-orcid":false,"given":"Agostino","family":"Di\u00a0Ciaula","sequence":"first","affiliation":[{"name":"Clinica Medica \u201cA. Murri\u201d, Department of Precision and Regenerative Medicine and Ionian Area (DiMePre\u2010J) University of Bari \u201cAldo Moro\u201d Medical School  Bari Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonilde","family":"Bonfrate","sequence":"additional","affiliation":[{"name":"Clinica Medica \u201cA. Murri\u201d, Department of Precision and Regenerative Medicine and Ionian Area (DiMePre\u2010J) University of Bari \u201cAldo Moro\u201d Medical School  Bari Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harshitha","family":"Shanmugam","sequence":"additional","affiliation":[{"name":"Clinica Medica \u201cA. 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