{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:17:57Z","timestamp":1791908277935,"version":"4.3.4"},"reference-count":38,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,4,4]],"date-time":"2024-04-04T00:00:00Z","timestamp":1712188800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is a frequent clinical condition globally. Single nucleotide polymorphisms (SNPs) associated with NAFLD have been proposed in the literature and based on bioinformatic screening. The association between NAFLD and genetic variants in Egyptians is still unclear. Hence, we sought to investigate the association of some genetic variants with NAFLD in Egyptians. Egyptians have been categorized into either the MASLD group (n = 205) or the healthy control group (n = 187). The severity of hepatic steatosis and liver fibrosis was assessed by a Fibroscan device. TaqMan-based genotyping assays were employed to explore the association of selected SNPs with MASLD. PNPLA3 rs738409 C&gt;G variant is associated with the presence of MASLD with liver fibrosis, the severity of both hepatic steatosis and liver fibrosis, increased systolic and diastolic blood pressure and increased alanine aminotransferase (all p &lt; 0.05), while the TM6SF2 rs58542926 C&gt;T, HSD17B13 rs9992651 G&gt;A, and GCKR rs1260326 T&gt;C variants were not (all p &gt; 0.05). The TM6SF2 rs58542926 T allele is associated with increased fasting blood glucose and a decreased waist circumference. The GCKR rs1260326 C allele is associated with decreased aspartate transaminase and diastolic blood pressure (all p &lt; 0.05). Only after adjusting for the risk factors (age, sex, BMI, WC, HDL, TG, diabetes mellitus, and hypertension) F2 liver fibrosis score is negatively correlated with the HSD17B13 rs9992651 GA genotype. This study offers evidence for the association of the PNPLA3 rs738409 C&gt;G variant with MASLD among Egyptians and for the association of the PNPLA3 rs738409 G allele, the TM6SF2 rs58542926 T allele, and the GCKR rs1260326 C allele with some parameters of cardiometabolic criteria.<\/jats:p>","DOI":"10.3390\/genes15040455","type":"journal-article","created":{"date-parts":[[2024,4,4]],"date-time":"2024-04-04T00:42:26Z","timestamp":1712191346000},"page":"455","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Relevance of PNPLA3, TM6SF2, HSD17B13, and GCKR Variants to MASLD Severity in an Egyptian Population"],"prefix":"10.3390","volume":"15","author":[{"given":"Nehal","family":"Elmansoury","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Biochemistry, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed A.","family":"Megahed","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0957-0977","authenticated-orcid":false,"given":"Ahmed","family":"Kamal","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Hepatology, Faculty of Medicine, Alexandria University, Alexandria 21131, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6675-234X","authenticated-orcid":false,"given":"Nefertiti","family":"El-Nikhely","sequence":"additional","affiliation":[{"name":"Institute of Graduate Studies and Research, Alexandria University, Alexandria 21526, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4108-4090","authenticated-orcid":false,"given":"Marina","family":"Labane","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manal","family":"Abdelmageed","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Internal Medicine, Medical Research Institute, Alexandria University, Alexandria 21561, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann K.","family":"Daly","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, Faculty of Medical Sciences, The Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Wahid","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biochemistry, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.1097\/HEP.0000000000000520","article-title":"A multisociety Delphi consensus statement on new fatty liver disease nomenclature","volume":"78","author":"Rinella","year":"2023","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1053\/j.gastro.2014.11.039","article-title":"Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States","volume":"148","author":"Wong","year":"2015","journal-title":"Gastroenterology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"14185","DOI":"10.3748\/wjg.v20.i39.14185","article-title":"Nonalcoholic fatty liver disease and aging: Epidemiology to management","volume":"20","author":"Bertolotti","year":"2014","journal-title":"World J. 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