TY - JOUR
T1 - Interaction Between Alcohol Consumption and PNPLA3 Variant in the Prevalence of Hepatic Steatosis in the US Population
AU - Lazo, Mariana
AU - Bilal, Usama
AU - Mitchell, Mack C.
AU - Potter, James
AU - Hernaez, Ruben
AU - Clark, Jeanne M.
N1 - Funding Information:
Funding This project was supported by a grant from the Alcoholic Beverage Medical Research Foundation to Mariana Lazo and by grant from the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK083393). The funders had no role in the design or conduct of the study, analysis or interpretation of the data, or preparation of the manuscript. Conflicts of Interest These authors disclose the following: Mariana Lazo reports grants from the Alcoholic Beverage Medical Research Foundation and the National Institutes of Health (during the conduct of the study). James Potter reports grants from National Institutes of Health (outside the submitted work). Mack C. Mitchell reports grants from Amygdala Neuroscience, Pfizer, Regeneron, the National Institute of Alcohol and Alcohol Abuse (outside the submitted work); and nonfinancial support from the Alcoholic Beverage Medical Research Foundation. Jeanne M. Clark and Ruben Hernaez report grants from the National Institutes of Health (both during the conduct of the study and outside the submitted work). The remaining author discloses no conflicts. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the U.S. government.
Publisher Copyright:
© 2021 AGA Institute
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
KW - Adults
KW - Alcohol Drinking
KW - Fatty Liver
KW - Genetic Predisposition to Disease
KW - Nutrition Surveys
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U2 - 10.1016/j.cgh.2020.08.054
DO - 10.1016/j.cgh.2020.08.054
M3 - Article
C2 - 32882427
AN - SCOPUS:85101025174
SN - 1542-3565
VL - 19
SP - 2606-2614.e4
JO - Clinical Gastroenterology and Hepatology
JF - Clinical Gastroenterology and Hepatology
IS - 12
ER -