title: Apolipoprotein E and protection against hepatitis E viral infection in American non-Hispanic blacks.
abstract: 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 ε3 and ε4 alleles of the apolipoprotein E (APOE) gene, encoding the apolipoprotein E protein that mediates lipoprotein metabolism. Seropositivity was significantly lower in participants carrying APOE ε4 (odds ratio=0.5, 95% CI 0.4-0.7; P=0.00004) and ε3 (odds ratio=0.6, 95% CI 0.4-0.8; P=0.001) compared to those carrying APOE ε2. 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.
  
  
  CONCLUSIONS
  Both 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.
authors.affiliation: Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA.
authors.forename: Lyna
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Research Data Center, National Center for Health Statistics, Centers for Disease Control and Prevention, Atlanta, GA.
authors.forename: Ajay
authors.initials: A
authors.lastname: Yesupriya
authors.affiliation: Office of Directors, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA.
authors.forename: Man-Huei
authors.initials: MH
authors.lastname: Chang
authors.affiliation: Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA.
authors.forename: Eyasu
authors.initials: E
authors.lastname: Teshale
authors.affiliation: Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA.
authors.forename: Chong-Gee
authors.initials: CG
authors.lastname: Teo
mesh_terms: D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000235:genetics; D000368:Aged; D001057:Apolipoproteins E / Q000235:genetics*; D002648:Child; D005260:Female; D016751:Hepatitis E / Q000208:ethnology* / Q000235:genetics; D006801:Humans; D008297:Male; D017058:Mexican Americans / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics
chemical_list: D001057:Apolipoproteins E