{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T06:20:43Z","timestamp":1790403643748,"version":"4.1.0"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":35,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:p>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\u2010HEV) 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\u2010Hispanic whites, 1919 non\u2010Hispanic blacks, and 1919 Mexican Americans from the Third National Health and Nutrition Examination Survey, 1991\u20101994. We studied 497 single\u2010nucleotide polymorphisms across 190 genes (particularly those associated with lipid metabolism). The genomic control method was used to adjust for potential population stratification. Non\u2010Hispanic blacks had the lowest seroprevalence of anti\u2010HEV immunoglobulin G (15.3%, 95% confidence interval [CI] 12.3%\u201019.0%) compared with non\u2010Hispanic whites (22.3%, 95% CI 19.1%\u201025.7%) and Mexican Americans (21.8%, 95% CI 19.0%\u201025.3%; <jats:italic toggle=\"yes\">P<\/jats:italic>\u2009&lt;\u20090.01). Non\u2010Hispanic blacks were the only population that showed association between anti\u2010HEV seropositivity and functional \u03b53 and \u03b54 alleles of the <jats:italic toggle=\"yes\">apolipoprotein E<\/jats:italic> (<jats:italic toggle=\"yes\">APOE<\/jats:italic>) gene, encoding the apolipoprotein E protein that mediates lipoprotein metabolism. Seropositivity was significantly lower in participants carrying <jats:italic toggle=\"yes\">APOE<\/jats:italic> \u03b54 (odds ratio\u2009=\u20090.5, 95% CI 0.4\u20100.7; <jats:italic toggle=\"yes\">P<\/jats:italic>\u2009=\u20090.00004) and \u03b53 (odds ratio\u2009=\u20090.6, 95% CI 0.4\u20100.8; <jats:italic toggle=\"yes\">P<\/jats:italic>\u2009=\u20090.001) compared to those carrying <jats:italic toggle=\"yes\">APOE<\/jats:italic> \u03b52. No significant associations were observed between other single\u2010nucleotide polymorphisms and anti\u2010HEV seropositivity in non\u2010Hispanic blacks or between any single\u2010nucleotide polymorphisms and anti\u2010HEV seropositivity in non\u2010Hispanic whites or Mexican Americans. <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>: Both <jats:italic toggle=\"yes\">APOE<\/jats:italic> \u03b53 and \u03b54 are significantly associated with protection against HEV infection in non\u2010Hispanic blacks; additional studies are needed to understand the basis of protection so that preventive services can be targeted to at\u2010risk persons. (H<jats:sc>epatology<\/jats:sc> 2015;62:1346\u20131352)<\/jats:p>","DOI":"10.1002\/hep.27938","type":"journal-article","created":{"date-parts":[[2015,6,19]],"date-time":"2015-06-19T19:15:24Z","timestamp":1434741324000},"page":"1346-1352","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":36,"title":["Apolipoprotein E and protection against hepatitis E viral infection in American non\u2010Hispanic blacks"],"prefix":"10.1097","volume":"62","author":[{"given":"Lyna","family":"Zhang","sequence":"first","affiliation":[{"name":"Division of Viral Hepatitis,National Center for HIV\/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention,Atlanta,GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajay","family":"Yesupriya","sequence":"additional","affiliation":[{"name":"Research Data Center, National Center for Health Statistics, Centers for Disease Control and Prevention,Atlanta,GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man\u2010Huei","family":"Chang","sequence":"additional","affiliation":[{"name":"Office of Directors, National Center for HIV\/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention,Atlanta,GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eyasu","family":"Teshale","sequence":"additional","affiliation":[{"name":"Division of Viral Hepatitis,National Center for HIV\/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention,Atlanta,GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong\u2010Gee","family":"Teo","sequence":"additional","affiliation":[{"name":"Division of Viral Hepatitis,National Center for HIV\/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention,Atlanta,GA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2015,7,28]]},"reference":[{"key":"hep27938-bib-0001-20241017","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1111\/j.1469-0691.2009.03111.x","article-title":"Much meat, much malady: changing perceptions of the epidemiology of hepatitis E","volume":"16","year":"2010","journal-title":"Clin Microbiol Infect"},{"key":"hep27938-bib-0002-20241017","doi-asserted-by":"crossref","first-page":"2477","DOI":"10.1016\/S0140-6736(11)61849-7","article-title":"Hepatitis E","volume":"379","year":"2012","journal-title":"Lancet"},{"key":"hep27938-bib-0003-20241017","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1002\/hep.25505","article-title":"The global burden of hepatitis E virus genotypes 1 and 2 in 2005","volume":"55","year":"2012","journal-title":"Hepatology"},{"key":"hep27938-bib-0005-20241017","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1017\/S0950268811002925","article-title":"Fatal outbreaks of jaundice in pregnancy and the epidemic history of hepatitis E","volume":"140","year":"2012","journal-title":"Epidemiol Infect"},{"key":"hep27938-bib-0006-20241017","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1097\/MOG.0b013e32835ff238","article-title":"Hepatitis E virus infection","volume":"29","year":"2013","journal-title":"Curr Opin Gastroenterol"},{"key":"hep27938-bib-0007-20241017","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1086\/599319","article-title":"Epidemiology of hepatitis E virus in the United States: results from the Third National Health and Nutrition Examination Survey, 1988\u20101994","volume":"200","year":"2009","journal-title":"J Infect Dis"},{"key":"hep27938-bib-0008-20241017","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1002\/hep.25513","article-title":"Variants in ABCB1, TGFB1, and XRCC1 genes and susceptibility to viral hepatitis A infection in Mexican Americans","volume":"55","year":"2012","journal-title":"Hepatology"},{"key":"hep27938-bib-0009-20241017","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1038\/ng.348","article-title":"A genome\u2010wide association study identifies variants in the HLA\u2010DP locus associated with chronic hepatitis B in Asians","volume":"41","year":"2009","journal-title":"Nat Genet"},{"key":"hep27938-bib-0010-20241017","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1038\/nature08463","article-title":"Genetic variation in IL28B and spontaneous clearance of hepatitis C virus","volume":"461","year":"2009","journal-title":"Nature"},{"key":"hep27938-bib-0011-20241017","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1053\/j.gastro.2012.01.046","article-title":"Genetic factors and hepatitis C virus infection","volume":"142","year":"2012","journal-title":"Gastroenterology"},{"key":"hep27938-bib-0012-20241017","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.tim.2013.10.005","article-title":"Peek\u2010a\u2010boo: membrane hijacking and the pathogenesis of viral hepatitis","volume":"22","year":"2014","journal-title":"Trends Microbiol"},{"key":"hep27938-bib-0013-20241017","doi-asserted-by":"crossref","first-page":"1880","DOI":"10.1099\/vir.0.010561-0","article-title":"ORF3 protein of hepatitis E virus is essential for virion release from infected cells","volume":"90","year":"2009","journal-title":"J Gen Virol"},{"key":"hep27938-bib-0014-20241017","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/1476-511X-9-5","article-title":"Impaired plasma lipid profiles in acute hepatitis","volume":"9","year":"2010","journal-title":"Lipids Health Dis"},{"key":"hep27938-bib-0015-20241017","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/1477-5956-9-5","article-title":"Plasma peptidome profiling of acute hepatitis E patients by MALDI\u2010TOF\/TOF","volume":"9","year":"2011","journal-title":"Proteome Sci"},{"key":"hep27938-bib-0016-20241017","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1111\/j.1574-695X.2010.00770.x","article-title":"Proteomic analysis of swine hepatitis E virus (sHEV)\u2013infected livers reveals upregulation of apolipoprotein and downregulation of ferritin heavy chain","volume":"61","year":"2011","journal-title":"FEMS Immunol Med Microbiol"},{"key":"hep27938-bib-0017-20241017","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1097\/HCO.0b013e328338574d","article-title":"Genetics of lipid disorders","volume":"25","year":"2010","journal-title":"Curr Opin Cardiol"},{"key":"hep27938-bib-0019-20241017","first-page":"54","article-title":"Prevalence in the United States of selected candidate gene variants: Third National Health and Nutrition Examination Survey, 1991\u20101994","volume":"169","year":"2009","journal-title":"Am J Epidemiol"},{"key":"hep27938-bib-0020-20241017","first-page":"1","article-title":"Plan and operation of the Third National Health and Nutrition Examination Survey, 1988\u201094. Series 1: programs and collection procedures","volume":"1","year":"1994","journal-title":"Vital Health Stat"},{"key":"hep27938-bib-0021-20241017","doi-asserted-by":"crossref","first-page":"279","DOI":"10.2307\/1402588","article-title":"On the variances of asymptotically normal estimators from complex surveys","volume":"51","year":"1983","journal-title":"International Statistical Review"},{"key":"hep27938-bib-0022-20241017","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1080\/01621459.1971.10482279","article-title":"A simple method for approximating the variance of a complicated estimate","volume":"66","year":"1971","journal-title":"J Am Stat Assoc"},{"key":"hep27938-bib-0023-20241017","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1038\/ng1104-1129","article-title":"Genomic control to the extreme","volume":"36","year":"2004","journal-title":"Nat Genet"},{"key":"hep27938-bib-0024-20241017","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: a practical and powerful approach to multiple testing","volume":"57","year":"1995","journal-title":"J R Stat Soc Series B Stat Methodol"},{"key":"hep27938-bib-0025-20241017","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1016\/S0022-2275(20)38094-9","article-title":"Proposed nomenclature of apoE isoproteins, apoE genotypes, and phenotypes","volume":"23","year":"1982","journal-title":"J Lipid Res"},{"key":"hep27938-bib-0026-20241017","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1146\/annurev.genom.1.1.507","article-title":"Apolipoprotein E: far more than a lipid transport protein","volume":"1","year":"2000","journal-title":"Annu Rev Genomics Hum Genet"},{"key":"hep27938-bib-0027-20241017","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/1476-511X-9-8","article-title":"Apolipoprotein E genotype and hepatitis C, HIV and herpes simplex disease risk: a literature review","volume":"9","year":"2010","journal-title":"Lipids Health Dis"},{"key":"hep27938-bib-0028-20241017","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/nature12415","article-title":"Integrative genomics identifies APOE epsilon4 effectors in Alzheimer's disease","volume":"500","year":"2013","journal-title":"Nature"},{"key":"hep27938-bib-0029-20241017","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1126\/science.3283935","article-title":"Apolipoprotein E: cholesterol transport protein with expanding role in cell biology","volume":"240","year":"1988","journal-title":"Science"},{"key":"hep27938-bib-0030-20241017","doi-asserted-by":"crossref","first-page":"E553","DOI":"10.1152\/ajpendo.1999.276.3.E553","article-title":"Comparison of the LDL\u2010receptor binding of VLDL and LDL from apoE4 and apoE3 homozygotes","volume":"276","year":"1999","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"hep27938-bib-0031-20241017","doi-asserted-by":"crossref","first-page":"41003","DOI":"10.1074\/jbc.M302267200","article-title":"Cellular binding of hepatitis C virus envelope glycoprotein E2 requires cell surface heparan sulfate","volume":"278","year":"2003","journal-title":"J Biol Chem"},{"key":"hep27938-bib-0032-20241017","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.plipres.2005.11.003","article-title":"Herpes simplex virus type 1, apolipoprotein E, and cholesterol: a dangerous liaison in Alzheimer's disease and other disorders","volume":"45","year":"2006","journal-title":"Prog Lipid Res"},{"key":"hep27938-bib-0033-20241017","doi-asserted-by":"crossref","first-page":"8718","DOI":"10.1073\/pnas.0803526105","article-title":"Apolipoprotein (apo) E4 enhances HIV\u20101 cell entry in vitro, and the APOE epsilon4\/epsilon4 genotype accelerates HIV disease progression","volume":"105","year":"2008","journal-title":"Proc Natl Acad Sci USA"},{"key":"hep27938-bib-0034-20241017","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1084\/jem.184.5.1699","article-title":"Dual interaction of the malaria circumsporozoite protein with the low density lipoprotein receptor\u2013related protein (LRP) and heparan sulfate proteoglycans","volume":"184","year":"1996","journal-title":"J Exp Med"},{"key":"hep27938-bib-0035-20241017","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0022-2275(20)33334-4","article-title":"Remnant lipoprotein metabolism: key pathways involving cell\u2010surface heparan sulfate proteoglycans and apolipoprotein E","volume":"40","year":"1999","journal-title":"J Lipid Res"},{"key":"hep27938-bib-0036-20241017","doi-asserted-by":"crossref","first-page":"12714","DOI":"10.1128\/JVI.00717-09","article-title":"Heparan sulfate proteoglycans are required for cellular binding of the hepatitis E virus ORF2 capsid protein and for viral infection","volume":"83","year":"2009","journal-title":"J Virol"},{"key":"hep27938-bib-0037-20241017","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1007\/s00705-013-1912-3","article-title":"The membrane on the surface of hepatitis E virus particles is derived from the intracellular membrane and contains trans\u2010Golgi network protein 2","volume":"159","year":"2014","journal-title":"Arch Virol"},{"key":"hep27938-bib-0038-20241017","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1089\/088922203322280900","article-title":"Lipid rafts and HIV pathogenesis: virion\u2010associated cholesterol is required for fusion and infection of susceptible cells","volume":"19","year":"2003","journal-title":"AIDS Res Hum Retroviruses"},{"key":"hep27938-bib-0039-20241017","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1002\/hep.24738","article-title":"Hepatitis E virus (HEV)\u2013specific T\u2010cell responses are associated with control of HEV infection","volume":"55","year":"2012","journal-title":"Hepatology"},{"key":"hep27938-bib-0040-20241017","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1002\/gepi.20379","article-title":"A critical evaluation of genomic control methods for genetic association studies","volume":"33","year":"2009","journal-title":"Genet Epidemiol"},{"key":"hep27938-bib-0041-20241017","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1046\/j.1469-1809.2000.6420171.x","article-title":"Estimation of admixture and detection of linkage in admixed populations by a Bayesian approach: application to African\u2010American populations","volume":"64","year":"2000","journal-title":"Ann Hum Genet"},{"key":"hep27938-bib-0042-20241017","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1002\/gepi.20079","article-title":"Genetic admixture and asthma\u2010related phenotypes in Mexican American and Puerto Rican asthmatics","volume":"29","year":"2005","journal-title":"Genet Epidemiol"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.27938","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-201511000-00007","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T00:12:43Z","timestamp":1729210363000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-201511000-00007"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,7,28]]},"references-count":40,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2015]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.27938","relation":{},"ISSN":["0270-9139","1527-3350"],"issn-type":[{"value":"0270-9139","type":"print"},{"value":"1527-3350","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,7,28]]},"assertion":[{"value":"2014-09-23","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-06-02","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}