Polymorphisms in the novel gene acyloxyacyl hydroxylase (AOAH) are associated with asthma and associated phenotypes.
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.
Barnes
Kathleen C
KC
Division of Allergy and Clinical Immunology, Department of Medicine, The Johns Hopkins University, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA. kbarnes@jhmi.edu
Grant
Audrey
A
Gao
Peisong
P
Baltadjieva
Daniela
D
Berg
Tiina
T
Chi
Peter
P
Zhang
Shu
S
Zambelli-Weiner
April
A
Ehrlich
Eva
E
Zardkoohi
Omeed
O
Brummet
Mary E
ME
Stockton
Maria
M
Watkins
Tonya
T
Gao
Li
L
Gittens
Marquita
M
Wills-Karp
Marsha
M
Cheadle
Christopher
C
Beck
Lisa A
LA
Beaty
Terri H
TH
Becker
Kevin G
KG
Garcia
Joe G N
JG
Mathias
Rasika A
RA
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
D018793:Interleukin-13; D018950:Lipopolysaccharide Receptors; D007073:Immunoglobulin E; D007371:Interferon-gamma; D002265:Carboxylic Ester Hydrolases; C048964:acyloxyacyl hydrolase