Date of this Version
Hepatology Volume 62, Issue 5, November 2015, Pages: 1346–1352
Hepatitis E viral (HEV) infection imposes a heavy health burden worldwide and is common in the United States. Previous investigations of risks addressed environmental and host behavioral/ lifestyle factors, but host genetic factors have not been examined. We assessed strength of associations between antibody to HEV (anti-HEV) immunoglobulin G seropositivity indicating past or recent HEV infection and human genetic variants among three major racial/ ethnic populations in the United States, involving 2434 non-Hispanic whites, 1919 non- Hispanic blacks, and 1919 Mexican Americans from the Third National Health and Nutrition Examination Survey, 1991-1994. We studied 497 single-nucleotide polymorphisms across 190 genes (particularly those associated with lipid metabolism). The genomic control method was used to adjust for potential population stratification. Non-Hispanic blacks had the lowest seroprevalence of anti-HEV immunoglobulin G (15.3%, 95% confidence interval [CI] 12.3%-19.0%) compared with non-Hispanic whites (22.3%, 95% CI 19.1%-25.7%) and Mexican Americans (21.8%, 95% CI 19.0%-25.3%; P < 0.01). Non-Hispanic blacks were the only population that showed association between anti-HEV seropositivity and functional Ɛ3 and Ɛ4 alleles of the apolipoprotein E (APOE) gene, encoding the apolipoprotein E protein thatmediates lipoprotein metabolism. Seropositivity was significantly lower in participants carrying APOE Ɛ4 (odds ratio50.5, 95% CI 0.4-0.7; P50.00004) and Ɛ3 (odds ratio50.6, 95% CI 0.4-0.8; P50.001) compared to those carrying APOE Ɛ2. No significant associations were observed between other single-nucleotide polymorphisms and anti-HEV seropositivity in non-Hispanic blacks or between any single-nucleotide polymorphisms and anti-HEV seropositivity in non-Hispanic whites or Mexican Americans. Conclusion: Both APOE Ɛ3 and Ɛ4 are significantly associated with protection against HEV infection in non- Hispanic blacks; additional studies are needed to understand the basis of protection so that preventive services can be targeted to at-risk persons.