Cholesteryl ester transfer protein gene variants and metabolic dysfunction-associated steatotic liver disease: genetic associations with steatosis in obese and lean individuals

Abstract Background and aims Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global health burden. While metabolic and lifestyle factors are central to its development, genetic predispositions also play a role. Variants in the cholesteryl ester transfer protein (CETP) gene, involved in lipid metabolism, may influence MASLD susceptibility. This study aims to investigate the role of CETP gene variants in MASLD, aiming to uncover genetic links to steatosis development. Methods This study is a case-control study. A total of 100 participants (80 MASLD patients and 20 controls) were categorized into four groups: obese diabetic, obese non-diabetic, lean diabetic, and lean non-diabetic. All were recruited from Minia University’s outpatient clinic between 2021 and 2022. Demographic, clinical, and genetic data were collected. Results Of 100 subjects, 70% were female, and 28% had hypertension. Lipid profiles showed significant differences in total cholesterol and triglycerides ( P < 0.001). The mutant CETP genotype (AA) was more common in lean nondiabetic individuals, whereas the wild-type CC was predominant in obese diabetic patients ( P < 0.001). Wild-type CC correlated with higher hepatic steatosis index (HSI) and fatty liver index (FLI) values, indicating more severe steatosis. In contrast, the AA genotype was associated with lower HSI and FLI scores ( P < 0.001). Conclusion CETP gene variants influence MASLD severity, especially in metabolically distinct groups. The wild-type CC is linked to higher HSI and FLI scores, indicating more severe steatosis in obese diabetics, while the mutant (AA) genotype correlates with lower indices, suggesting protection in lean nondiabetic individuals.