Interaction between alcohol consumption and PNPLA3 variant in the prevalence of hepatic steatosis in the U.S. Population.
To our knowledge, the interaction between alcohol consumption and PNPLA3 genotype on hepatic steatosis has not been explored in a representative sample. To examine the interaction between alcohol consumption and PNPLA3 genotype on hepatic steatosis in the U.S. adult population.Cross-sectional study of 4,674 adult participants of the Third National Health and Nutrition Examination Survey, Phase 2 (1991-1994) with data on PNPLA3 genotype, self-reported alcohol consumption, ultrasound-defined hepatic steatosis and socio-demographic characteristics.In 1991-1994 in the U.S. population, the weighted allele frequency of the G (risk) allele of the rs738409 at PNPLA3 was 25.4%. We confirmed both a J shaped association between alcohol consumption and hepatic steatosis among those with the CC genotype of PNPLA3, and a higher prevalence of hepatic steatosis among those with PNPLA3 gene G variant. We found evidence of an interaction of PNPLA3 G allele presence on the association between moderate alcohol consumption and hepatic steatosis on both the multiplicative (relative prevalence ratio [RPR]=1.95, 95% confidence interval [CI] 1.04-3.65) and additive scales (relative excess risk due to interaction=0.49, 95% CI 0.13-0.85). Compared to never drinkers, moderate alcohol drinking was associated with a 48% decreased risk of hepatic steatosis only among those without PNPLA3 G allele (PR=0.52, 95% CI 0.26-1.05), with no association among those with at least one copy of the PNPLA3 G allele (PR=1.02, 95% CI 0.68-1.54).Our results suggest that a highly common and strong genetic susceptibility to liver disease is modifiable by the level of alcohol consumption. Keeping alcohol consumption low may offset genetic predisposition to liver disease.