title: Variants in ABCB1, TGFB1, and XRCC1 genes and susceptibility to viral hepatitis A infection in Mexican Americans.
abstract: Hepatitis A vaccination has dramatically reduced the incidence of hepatitis A virus (HAV) infection, but new infections continue to occur. To identify human genetic variants conferring a risk for HAV infection among the three major racial/ethnic populations in the United States, we assessed associations between 67 genetic variants (single nucleotide polymorphisms [SNPs]) among 31 candidate genes and serologic evidence of prior HAV infection using a population-based, cross-sectional study of 6,779 participants, including 2,619 non-Hispanic whites, 2,095 non-Hispanic blacks, and 2,065 Mexican Americans enrolled in phase 2 (1991-1994) of the Third National Health and Nutrition Examination Survey. Among the three racial/ethnic groups, the number (weighted frequency) of seropositivity for antibody to HAV was 958 (24.9%), 802 (39.2%), and 1540 (71.5%), respectively. No significant associations with any of the 67 SNPs were observed among non-Hispanic whites or non-Hispanic blacks. In contrast, among Mexican Americans, variants in two genes were found to be associated with an increased risk of HAV infection: TGFB1 rs1800469 (adjusted odds ratio [OR], 1.38; 95% confidence interval [CI], 1.14-1.68; P value adjusted for false discovery rate [FDR-P] = 0.017) and XRCC1 rs1799782 (OR, 1.57; 95% CI, 1.27-1.94; FDR-P = 0.0007). A decreased risk was found with ABCB1 rs1045642 (OR, 0.79; 95% CI, 0.71-0.89; FDR-P = 0.0007).
  
  
  CONCLUSIONS
  Genetic variants in ABCB1, TGFB1, and XRCC1 appear to be associated with susceptibility to HAV infection among Mexican Americans. Replication studies involving larger population samples are warranted.
authors.affiliation: Office of Public Health Genomics, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Diseases Control and Prevention, 1600 Clifton Road NE, Atlanta, GA 30333, USA. chn6@cdc.gov
authors.forename: Lyna
authors.initials: L
authors.lastname: Zhang
authors.forename: Ajay
authors.initials: A
authors.lastname: Yesupriya
authors.forename: Dale J
authors.initials: DJ
authors.lastname: Hu
authors.forename: Man-Huei
authors.initials: MH
authors.lastname: Chang
authors.forename: Nicole F
authors.initials: NF
authors.lastname: Dowling
authors.forename: Renée M
authors.initials: RM
authors.lastname: Ned
authors.forename: Venkatachalam
authors.initials: V
authors.lastname: Udhayakumar
authors.forename: Mary Lou
authors.initials: ML
authors.lastname: Lindegren
authors.forename: Yury
authors.initials: Y
authors.lastname: Khudyakov
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044383:Black People / Q000208:ethnology / Q000235:genetics; D002648:Child; D003430:Cross-Sectional Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006506:Hepatitis A / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D030041:Hepatitis A virus; D006801:Humans; D008297:Male; D017058:Mexican Americans / Q000208:ethnology / Q000235:genetics*; D008875:Middle Aged; D009749:Nutrition Surveys; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D053773:Transforming Growth Factor beta1 / Q000235:genetics*; D014481:United States; D044465:White People / Q000208:ethnology / Q000235:genetics; D000076105:X-ray Repair Cross Complementing Protein 1; D055815:Young Adult; D001741:Black or African American
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004268:DNA-Binding Proteins; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human