biostudies-literatureUnknown8(5)Hehl L<h4>Background</h4>Common variants of the max-like protein X (MLX)-interacting protein-like (MLXIPL) gene, encoding the transcription factor carbohydrate-responsive element-binding protein, have been shown to be associated with plasma triglyceride levels. However, the role of these variants in steatotic liver disease (SLD) is unclear.<h4>Methods</h4>We used a genome-first approach to analyze a variety of metabolic phenotypes and clinical outcomes associated with a common missense variant in MLXIPL, Gln241His, in 2 large biobanks: the UK Biobank and the Penn Medicine Biobank.<h4>Results</h4>Carriers of MLXIPL Gln241His were associated with significantly lower serum levels of triglycerides, apolipoprotein-B, gamma-glutamyl transferase, and alkaline phosphatase. Additionally, MLXIPL Gln241HisHepatology communicationse0427https://www.ebi.ac.uk/biostudies/studies/S-EPMC12333743biostudies-literatureA genome-first approach to variants in MLXIPL and their association with hepatic steatosis and plasma lipids.PMC12333743Rader DJTrautwein CVell MSSchneider CVVujkovic MCreasy KTSeeling KSVitali CHehl LScorletti EConlon DZandvakili IRegeneron Genetics CenterRendel MDSchneider KMfalseA genome-first approach to variants in MLXIPL and their association with hepatic steatosis and plasma lipids.<h4>Background</h4>Common variants of the max-like protein X (MLX)-interacting protein-like (MLXIPL) gene, encoding the transcription factor carbohydrate-responsive element-binding protein, have been shown to be associated with plasma triglyceride levels. However, the role of these variants in steatotic liver disease (SLD) is unclear.<h4>Methods</h4>We used a genome-first approach to analyze a variety of metabolic phenotypes and clinical outcomes associated with a common missense variant in MLXIPL, Gln241His, in 2 large biobanks: the UK Biobank and the Penn Medicine Biobank.<h4>Results</h4>Carriers of MLXIPL Gln241His were associated with significantly lower serum levels of triglycerides, apolipoprotein-B, gamma-glutamyl transferase, and alkaline phosphatase. Additionally, MLXIPL Gln241His2024-01-01T00:00:00Z2024 May2026-04-15T19:17:02.702Z2026-04-07T14:01:13.515ZS-EPMC123337433866873110.1097/HC9.0000000000000427