The Interplay of Genetics and Lifestyle in MASLD: Focus on LPIN1 rs13412852 and Sedentary Behaviour

The LPIN1 rs13412852 variant has been linked to lipid levels and liver disease in children. This genotype may modulate the liver's response to sedentary behaviour, potentially increasing the vulnerability of certain individuals to liver dysfunction. These findings underscore the need to consider both genetic predisposition and environmental exposures when evaluating disease risk. This study aims to investigate the association between the LPIN rs13412852 T-allele and sedentary behaviour and to explore how the interplay between genetic and environmental factors may contribute to individual susceptibility to liver-related conditions. rs13412852 was genotyped in a cohort from Southern Italy (n = 394), and all participants were administered an International Physical Activity Questionnaire (IPAQ), collected a blood sample, and underwent an abdominal ultrasound analysis. The association between metabolic dysfunction-associated steatotic liver disease (MASLD), rs13412852, and sedentary behaviour, alone and together with interaction, was studied. The results indicated a statistical association on MASLD, of rs13412852, and sedentary levels (OR = 1.80, 1.06 to 3.05 95% C.I., p = 0.03, and OR = 1.72, 1.13 to 2.64 95% C.I.), respectively, and also with interaction between moderate or sever sedentary level and T-carrier (OR = 2.99, 1.39 to 6.45 95% C.I., p = 0.005) adjusted for some covariates. The risk of MASLD was highest among individuals with both moderate/severe sedentary behaviour and the CT/TT genotype, suggesting a potential synergistic effect. These findings establish LPIN1 as both a physiological gatekeeper and a genetic susceptibility locus, with its influence subject to modification via behavioural treatments.