Apolipoprotein E and protection against hepatitis E virus infection in American, non-Hispanic blacks.

Zhang L1,2, Yesupriya A3, Chang MH4, Teshale E1, Teo CG1.

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Abstract

Hepatitis E virus (HEV) infection imposes a heavy health burden worldwide and is common in the United States. Previous investigations of risks address environmental and host behavioral/lifestyle factors, but host genetic factors have not been examined. We assessed strength of associations between anti-HEV IgG 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 (SNPs) across 190 genes (particularly those associated with lipid metabolism). Genomic control method was used to adjust for potential population stratification. Non-Hispanic blacks had the lowest seroprevalence of anti-HEV IgG (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 ε3 and ε4 alleles of apolipoprotein E (APOE) gene, encoding apolipoprotein E protein that mediates lipoprotein metabolism. Seropositivity was significantly lower in participants carrying APOE ε4 (odds ratio [OR], 0.5; 95%CI, 0.4-0.7; P = 0.00004) and ε3 (OR, 0.6; 95%CI, 0.4-0.8; P = 0.001) compared to those carrying APOE ε2. No significant associations were observed between other SNPs and anti-HEV seropositivity in non-Hispanic blacks or between any SNPs and anti-HEV seropositivity in non-Hispanic whites or Mexican Americans.

CONCLUSION:

APOE ε3 and ε4 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. This article is protected by copyright. All rights reserved.