Author information
1Department of Community Health and Prevention, Dornsife School of Public Health, Drexel University, Philadelphia, Pennsylvania; Urban Health Collaborative, Dornsife School of Public Health, Drexel University, Philadelphia, Pennsylvania; Division of General Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: mariana.lazoelizondo@drexel.edu.
2Urban Health Collaborative, Dornsife School of Public Health, Drexel University, Philadelphia, Pennsylvania; Department of Epidemiology and Biostatistics, Dornsife School of Public Health, Drexel University, Philadelphia, Pennsylvania.
3Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
4Division of Gastroenterology & Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
5Section of Gastroenterology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas; Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas; Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas.
6Division of General Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland; Division of Gastroenterology & Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Abstract
Background & aims: 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 US adult population.
Methods: 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.
Results: 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).
Conclusions: 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.