Dataset Information

The immunity-related GTPase M rs13361189 variant does not increase the risk for prevalent or incident steatosis; results from the Framingham Heart Study.

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.

SUBMITTER: Simon TG

PROVIDER: S-EPMC6535115 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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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.

Simon Tracey G TG Deng Xuan X Liu Ching-Ti CT Chung Raymond T RT Long Michelle T MT

Liver international : official journal of the International Association for the Study of the Liver 20190217 6

<h4>Background & aims</h4>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.<h4>Methods</h4>We included all Framingham Heart Study participants with available data on the IRGM rs13361189 variant, undergoing study-directed computed tomog ...[more]

PMID: 30597691

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Project description:BackgroundThere have been conflicting reported associations between dietary factors and incident atrial fibrillation (AF).ObjectiveWe evaluated associations between consumption of alcohol, caffeine, fiber, and polyunsaturated fatty acids (PUFAs) and incident AF in the Framingham Heart Study.DesignParticipants without AF (n = 4526; 9640 examinations; mean age: 62 y; 56% women) from the original and offspring cohorts completed food-frequency questionnaires and were followed prospectively for 4 y. We examined the associations between dietary exposures and AF with Cox proportional hazards regression.ResultsA total of 296 individuals developed AF (177 men, 119 women). In multivariable analyses, there were no significant associations between examined dietary exposures and AF risk. Hazard ratios (HRs) for increasing quartiles of dietary factors were as follows: for alcohol, 0.73 (95% CI: 0.5, 1.05), 0.85 (95% CI: 0.61, 1.18), and 1.12 (95% CI: 0.83, 1.51) (P for trend = 0.48); for caffeine, 0.84 (95% CI: 0.62, 1.15), 0.87 (95% CI: 0.64, 1.2), and 0.98 (95% CI: 0.7, 1.39) (P for trend = 0.84); for total fiber, 0.86 (95% CI: 0.61, 1.2), 0.64 (95% CI: 0.44, 0.92), and 0.81 (95% CI: 0.54, 1.2) (P for trend = 0.16); and for n-3 (omega-3) PUFAs, 1.11 (95% CI: 0.81, 1.54), 0.92 (95% CI: 0.65, 1.29), and 1.18 (95% CI: 0.85, 1.64) (P for trend = 0.57; quartile 1 was the reference group). In exploratory analyses, consumption of >4 servings of dark fish/wk (5 cases and 21 individuals at risk) was significantly associated with AF risk compared with the consumption of <1 serving of dark fish/wk (HR: 6.53; 95% CI: 2.65, 16.06; P < 0.0001).ConclusionsConsumption of alcohol, caffeine, fiber, and fish-derived PUFAs was not significantly associated with AF risk. The observed adverse association between the consumption of dark fish and AF merits further investigation. Our findings suggest that the dietary exposures examined convey limited attributable risk of AF in the general population.

Project description:BackgroundRemnant lipoproteins (RLPs), the triglyceride-enriched precursors to low-density lipoprotein, are an emerging risk factor for coronary heart disease (CHD). We sought to determine the association of RLP cholesterol (RLP-C) levels with incident CHD in 2 diverse, prospective, longitudinal observational US cohorts.Methods and resultsWe analyzed cholesterol levels from serum lipoprotein samples separated via density gradient ultracentrifugation in 4114 US black participants (mean age 53.8 years, 64% women) from the Jackson Heart Study and a random sample of 818 predominantly white participants (mean age 57.3 years, 52% women) from the Framingham Offspring Cohort Study. Multivariable-adjusted hazard ratios (HRs) for RLP-C (the sum of very low-density lipoprotein3 cholesterol and intermediate-density lipoprotein cholesterol) were derived to estimate associations with incident CHD events consisting of myocardial infarction, CHD death, and revascularizations for each cohort separately and as a combined population. There were 146 CHD events in the combined population. After adjustments for age, sex, body mass index, smoking, blood pressure, diabetes, and lipid-lowering therapy for the combined population, RLP-C (HR 1.23 per 1-SD increase, 95% CI 1.06-1.42, P<0.01) and intermediate-density lipoprotein cholesterol (HR 1.26 per 1-SD increase, 95% CI 1.08-1.47, P<0.01) predicted CHD during an 8-year follow-up. Associations were attenuated by high-density lipoprotein cholesterol and ultimately lost significance with inclusion of real low-density lipoprotein cholesterol, which excludes Lp(a) and IDL cholesterol fractions. Similar associations were seen in multivariable analyses within each cohort.ConclusionRLP-C levels are predictive of incident CHD in this diverse group of primary prevention subjects. Interventions aimed at reducing RLP-C to prevent CHD warrant further intensive investigation.Clinical trial registrationURL: http://www.ClinicalTrials.gov. Unique identifier: NCT00415415.

Dataset Information

The immunity-related GTPase M rs13361189 variant does not increase the risk for prevalent or incident steatosis; results from the Framingham Heart Study.

Publications

The immunity-related GTPase M rs13361189 variant does not increase the risk for prevalent or incident steatosis; results from the Framingham Heart Study.

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