Tracey G Simon1,2, Xuan Deng3, Ching-Ti Liu3, Raymond T Chung1,2, Michelle T Long4. 1. Liver Center, Division of Gastroenterology, Department of Medicine, Massachusetts General, Hospital, Boston, Massachusetts. 2. Harvard Medical School, Boston, Massachusetts. 3. Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts. 4. Evans Department of Medicine, Section of Gastroenterology, Boston University School of Medicine, Boston, Massachusetts.
Abstract
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.
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 IRGMrs13361189 variants and NAFLD in a community-based cohort of adults. METHODS: We included all Framingham Heart Study participants with available data on the IRGMrs13361189 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 IRGMrs13361189 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.
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