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The immunity‐related GTPase M rs13361189 variant does not increase the risk for prevalent or incident steatosis; results from the Framingham Heart Study
Author(s) -
Simon Tracey G.,
Deng Xuan,
Liu ChingTi,
Chung Raymond T.,
Long Michelle T.
Publication year - 2019
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.14039
Subject(s) - medicine , genotype , odds ratio , nonalcoholic fatty liver disease , framingham heart study , cohort , logistic regression , framingham risk score , steatosis , gastroenterology , fatty liver , disease , genetics , biology , gene
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.