title: Evaluation of genetic susceptibility to childhood allergy and asthma in an African American urban population.
abstract: BACKGROUND
  Asthma and allergy represent complex phenotypes, which disproportionately burden ethnic minorities in the United States. Strong evidence for genomic factors predisposing subjects to asthma/allergy is available. However, methods to utilize this information to identify high risk groups are variable and replication of genetic associations in African Americans is warranted.
  
  
  METHODS
  We evaluated 41 single nucleotide polymorphisms (SNP) and a deletion corresponding to 11 genes demonstrating association with asthma in the literature, for association with asthma, atopy, testing positive for food allergens, eosinophilia, and total serum IgE among 141 African American children living in Detroit, Michigan. Independent SNP and haplotype associations were investigated for association with each trait, and subsequently assessed in concert using a genetic risk score (GRS).
  
  
  RESULTS
  Statistically significant associations with asthma were observed for SNPs in GSTM1, MS4A2, and GSTP1 genes, after correction for multiple testing. Chromosome 11 haplotype CTACGAGGCC (corresponding to MS4A2 rs574700, rs1441586, rs556917, rs502581, rs502419 and GSTP1 rs6591256, rs17593068, rs1695, rs1871042, rs947895) was associated with a nearly five-fold increase in the odds of asthma (Odds Ratio (OR) = 4.8, p = 0.007). The GRS was significantly associated with a higher odds of asthma (OR = 1.61, 95% Confidence Interval = 1.21, 2.13; p = 0.001).
  
  
  CONCLUSIONS
  Variation in genes associated with asthma in predominantly non-African ethnic groups contributed to increased odds of asthma in this African American study population. Evaluating all significant variants in concert helped to identify the highest risk subset of this group.
authors.affiliation: US Environmental Protection Agency (EPA), National Exposure Research Laboratory, Durham, NC, USA. brjoubert@gmail.com
authors.forename: Bonnie R
authors.initials: BR
authors.lastname: Joubert
authors.forename: David M
authors.initials: DM
authors.lastname: Reif
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Edwards
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Leiner
authors.forename: Edward E
authors.initials: EE
authors.lastname: Hudgens
authors.forename: Peter
authors.initials: P
authors.lastname: Egeghy
authors.forename: Jane E
authors.initials: JE
authors.lastname: Gallagher
authors.forename: Elaine Cohen
authors.initials: EC
authors.lastname: Hubal
mesh_terms: D000293:Adolescent; D001741:Black or African American / Q000235:genetics*; D001249:Asthma / Q000235:genetics*; D002648:Child; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D003430:Cross-Sectional Studies; D005260:Female; D005512:Food Hypersensitivity / Q000235:genetics; D020022:Genetic Predisposition to Disease; D051549:Glutathione S-Transferase pi / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics*; D006969:Hypersensitivity, Immediate / Q000235:genetics; D015810:Linkage Disequilibrium; D008297:Male; D008824:Michigan; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D017455:Receptors, IgE / Q000235:genetics; D012307:Risk Factors; D017384:Sequence Deletion; D014505:Urban Population
chemical_list: D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D017455:Receptors, IgE; C502447:MS4A2 protein, human; C496556:GSTP1 protein, human