Polymorphisms in the novel gene acyloxyacyl hydroxylase (AOAH) are associated with asthma and associated phenotypes

Kathleen C. Barnes, Audrey Grant, Peisong Gao, Daniela Baltadjieva, Tiina Berg, Peter Chi, Shu Zhang, April Zambelli-Weiner, Eva Ehrlich, Omeed Zardkoohi, Mary E. Brummet, Maria Stockton, Tonya Watkins, Li Gao, Marquita Gittens, Marsha Wills-Karp, Christopher Cheadle, Lisa A. Beck, Terri H. Beaty, Kevin G. BeckerJoe G.N. Garcia, Rasika A. Mathias

Research output: Contribution to journalArticle

31 Scopus citations

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-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.

Original languageEnglish (US)
Pages (from-to)70-77
Number of pages8
JournalJournal of Allergy and Clinical Immunology
Volume118
Issue number1
DOIs
StatePublished - Jul 1 2006
Externally publishedYes

Keywords

  • CD14
  • acyloxyacyl hydroxylase
  • association
  • asthma
  • family-based association test
  • soluble CD14
  • total IgE

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Barnes, K. C., Grant, A., Gao, P., Baltadjieva, D., Berg, T., Chi, P., Zhang, S., Zambelli-Weiner, A., Ehrlich, E., Zardkoohi, O., Brummet, M. E., Stockton, M., Watkins, T., Gao, L., Gittens, M., Wills-Karp, M., Cheadle, C., Beck, L. A., Beaty, T. H., ... Mathias, R. A. (2006). Polymorphisms in the novel gene acyloxyacyl hydroxylase (AOAH) are associated with asthma and associated phenotypes. Journal of Allergy and Clinical Immunology, 118(1), 70-77. https://doi.org/10.1016/j.jaci.2006.03.036