title: Polymorphisms in the novel gene acyloxyacyl hydroxylase (AOAH) are associated with asthma and associated phenotypes.
abstract: BACKGROUND
  The gene encoding acyloxyacyl hydroxylase (AOAH), an enzyme that hydrolyzes secondary fatty acyl chains of LPS, is localized on chromosome 7p14-p12, where evidence for linkage to total IgE (tIgE) concentrations and asthma has been previously reported.
  
  
  OBJECTIVE
  We hypothesized that variants in AOAH are associated with asthma and related phenotypes. Because both AOAH and soluble CD14 respond to LPS, we tested for gene-gene interaction.
  
  
  METHODS
  We investigated the association between 28 single nucleotide polymorphisms throughout the AOAH gene and asthma, concentrations of tIgE, the ratio of IL-13/IFN-gamma, and soluble CD14 levels among 125 African Caribbean, multiplex asthmatic pedigrees (n = 834). Real-time PCR was used to assess whether AOAH cDNA expression differed with AOAH genotype.
  
  
  RESULTS
  Significant effects were observed for all 4 phenotypes and AOAH markers in 3 distinct regions (promoter, introns 1-6, and the intron 12/exon 13 boundary/intron 13 region) by means of single-marker and haplotype analyses, with the strongest evidence for a 2-single-nucleotide-polymorphism haplotype and log[tIgE] (P = .006). There was no difference in AOAH expression levels by AOAH genotype for any of the markers. Comparing genotypic distributions at both the AOAH marker rs2727831 and CD14(-260)C >T raises the possibility of gene-gene interaction (P = .006-.036).
  
  
  CONCLUSIONS
  Our results indicate that polymorphisms in markers within the AOAH gene are associated with risk of asthma and associated quantitative traits (IgE and cytokine levels) among asthmatic subjects and their families in Barbados, and there is an interactive effect on tIgE and asthma concentrations between an AOAH marker and the functional CD14(-260)C >T polymorphism.
  
  
  CONCLUSIONS
  AOAH is a novel innate immunity candidate gene associated with asthma and related phenotypes in an African ancestry population.
authors.affiliation: Division of Allergy and Clinical Immunology, Department of Medicine, The Johns Hopkins University, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA. kbarnes@jhmi.edu
authors.forename: Kathleen C
authors.initials: KC
authors.lastname: Barnes
authors.forename: Audrey
authors.initials: A
authors.lastname: Grant
authors.forename: Peisong
authors.initials: P
authors.lastname: Gao
authors.forename: Daniela
authors.initials: D
authors.lastname: Baltadjieva
authors.forename: Tiina
authors.initials: T
authors.lastname: Berg
authors.forename: Peter
authors.initials: P
authors.lastname: Chi
authors.forename: Shu
authors.initials: S
authors.lastname: Zhang
authors.forename: April
authors.initials: A
authors.lastname: Zambelli-Weiner
authors.forename: Eva
authors.initials: E
authors.lastname: Ehrlich
authors.forename: Omeed
authors.initials: O
authors.lastname: Zardkoohi
authors.forename: Mary E
authors.initials: ME
authors.lastname: Brummet
authors.forename: Maria
authors.initials: M
authors.lastname: Stockton
authors.forename: Tonya
authors.initials: T
authors.lastname: Watkins
authors.forename: Li
authors.initials: L
authors.lastname: Gao
authors.forename: Marquita
authors.initials: M
authors.lastname: Gittens
authors.forename: Marsha
authors.initials: M
authors.lastname: Wills-Karp
authors.forename: Christopher
authors.initials: C
authors.lastname: Cheadle
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Beck
authors.forename: Terri H
authors.initials: TH
authors.lastname: Beaty
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Becker
authors.forename: Joe G N
authors.initials: JG
authors.lastname: Garcia
authors.forename: Rasika A
authors.initials: RA
authors.lastname: Mathias
mesh_terms: D001249:Asthma / Q000201:enzymology / Q000235:genetics* / Q000276:immunology; D002265:Carboxylic Ester Hydrolases / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007113:Immunity, Innate; D007073:Immunoglobulin E / Q000097:blood; D007371:Interferon-gamma / Q000097:blood; D018793:Interleukin-13 / Q000097:blood; D018950:Lipopolysaccharide Receptors / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide
chemical_list: D018793:Interleukin-13; D018950:Lipopolysaccharide Receptors; D007073:Immunoglobulin E; D007371:Interferon-gamma; D002265:Carboxylic Ester Hydrolases; C048964:acyloxyacyl hydrolase