TY - JOUR
T1 - Polymorphisms in the novel gene acyloxyacyl hydroxylase (AOAH) are associated with asthma and associated phenotypes
AU - Barnes, Kathleen C.
AU - Grant, Audrey
AU - Gao, Peisong
AU - Baltadjieva, Daniela
AU - Berg, Tiina
AU - Chi, Peter
AU - Zhang, Shu
AU - Zambelli-Weiner, April
AU - Ehrlich, Eva
AU - Zardkoohi, Omeed
AU - Brummet, Mary E.
AU - Stockton, Maria
AU - Watkins, Tonya
AU - Gao, Li
AU - Gittens, Marquita
AU - Wills-Karp, Marsha
AU - Cheadle, Christopher
AU - Beck, Lisa A.
AU - Beaty, Terri H.
AU - Becker, Kevin G.
AU - Garcia, Joe G.N.
AU - Mathias, Rasika A.
N1 - Funding Information:
Supported by National Institutes of Health (NIH) grants U01 HL66615, AI50024-03, and HL67736 and an Asthma and Allergy Foundation of America New Investigator Award Grant (KCB). K. C. B. was supported in part by the Mary Beryl Patch Turnbull Scholar Program, and R. A. M. was supported by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health.
PY - 2006/7
Y1 - 2006/7
N2 - 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-γ, 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). Conclusion: 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. Clinical implications: AOAH is a novel innate immunity candidate gene associated with asthma and related phenotypes in an African ancestry population.
AB - 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-γ, 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). Conclusion: 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. Clinical implications: AOAH is a novel innate immunity candidate gene associated with asthma and related phenotypes in an African ancestry population.
KW - CD14
KW - acyloxyacyl hydroxylase
KW - association
KW - asthma
KW - family-based association test
KW - soluble CD14
KW - total IgE
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U2 - 10.1016/j.jaci.2006.03.036
DO - 10.1016/j.jaci.2006.03.036
M3 - Article
C2 - 16815140
AN - SCOPUS:33745367667
SN - 0091-6749
VL - 118
SP - 70
EP - 77
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 1
ER -