Abstract P131: Influence of PNPLA3 Interaction With Physical Activity and Dietary Pattern on Hepatic Steatosis Among African Americans in the Jackson Heart Study

Abstract

Background: The genetic basis for nonalcoholic fatty liver disease (NAFLD) has been studied widely. Several common variants near genes known to be associated with NAFLD have been identified and replicated across ancestries. The extent to which these variants interact with lifestyles factors, particularly in African Americans (AAs) is unknown. We hypothesized that physical activity and dietary pattern moderate the association of patatin-like phospholipase domain containing 3 ( PNPLA3 ) variant rs738409 with NAFLD. Methods: Of the 2,884 Jackson Heart Study participants with hepatic steatosis measured by computed tomography, a subset of 1,075 were part of a family study and another set of 1,583 were genotyped for common genetic variants near PNPLA3 . We estimated polygenic heritability of hepatic steatosis (inverse normally transformed) using a variance components approach implemented in SOLAR controlling for variations in age, age 2 , gender and alcoholic drinks. To evaluate moderation effect of rs738409 by diet and physical activity, we analyzed genotyped individual using multiple linear regression and controlled for population structure in addition to covariates included in estimating heritability. Dietary pattern was defined using principal components analysis while physical activity according to AHA categorization. Results: The polygenic heritability estimate of hepatic steatosis in our study was 0.33±0.09 (p<0.001). The G allele of the rs738409 variant (allele frequency 14%) was significantly (beta ± standard error; p-value) associated with high hepatic steatosis in participants who are physically inactive (0.29±0.12; 0.0169) and those with unhealthy dietary pattern (0.25±0.10; 0.0144) ( Figure) . Conclusions: In a community-based cohort of AA, heritability of hepatic steatosis is moderate and compares favorably with previous estimates. Physical activity and diet modulates the effect of PNPLA3 : rs738409 on NALFD. The role lifestyle factors on NAFLD need to be validated in other population samples.