Background & aims: Emerging data from paediatric populations suggest that variants in the autophagy-governing immunity-related GTPase M (IRGM) gene may contribute to nonalcoholic fatty liver disease (NAFLD) susceptibility. We examined the relationship between IRGM rs13361189 variants and NAFLD in a community-based cohort of adults.
Methods: We included all Framingham Heart Study participants with available data on the IRGM rs13361189 variant, undergoing study-directed computed tomography (CT) scans of the abdomen (2002-2005). Using multivariable linear and logistic regression modelling, we evaluated cross-sectional associations between rs13361189 genotype and hepatic steatosis (HS). Among the subset of participants without baseline HS and who underwent follow-up CT scan between 2008 and 2011, we used multivariable logistic regression modelling to assess the longitudinal relationship between IRGM rs13361189 genotype and risk for incident HS.
Results: Among 2070 participants (50% women; mean age 51 ± 11 years), 332 (16%) had one copy of the variant rs13361189 variant C allele, while 19 (1%) had the CC genotype. Compared to the TT genotype, there was no increased odds of prevalent HS with the CT or CC genotype (multivariable-adjusted odds ratio [OR] 0.93 [95% CI 0.68-128] and 0.86 [95% CI 0.46-1.63], respectively). Among individuals without baseline HS (n = 1052), 19.3% developed incident HS over median 6.1 years. Compared to the TT genotype, neither the CT nor the CC genotype were significantly associated with incident HS (all P > 0.05).
Conclusion: In our community-based, longitudinal cohort of Caucasian adults, variants in the autophagy-governing IRGM gene at the rs13361189 locus were not associated with increased prevalent or incident HS.
Keywords: autophagy; gene variants; nonalcoholic fatty liver disease; steatosis.
© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.