Polymorphisms in the novel gene acyloxyacyl hydroxylase (AOAH) are associated with asthma and associated phenotypes - 17/08/11
, Audrey Grant, MS a, Peisong Gao, MD, PhD a, Daniela Baltadjieva, MD, PhD a, Tiina Berg, BS a, Peter Chi, MHS a, Shu Zhang, MA a, April Zambelli-Weiner, PhD a, Eva Ehrlich, MS a, Omeed Zardkoohi, MD d, Mary E. Brummet, MS a, Maria Stockton, MA a, Tonya Watkins, BS a, Li Gao, MD, PhD a, Marquita Gittens, PhD e, Marsha Wills-Karp, PhD f, Christopher Cheadle, PhD a, Lisa A. Beck, MD a, g, Terri H. Beaty, PhD b, Kevin G. Becker, PhD h, Joe G.N. Garcia, MD c, Rasika A. Mathias, ScD b, i
Reprint requests: Kathleen C. Barnes, PhD, The Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Rm 3A.62, Baltimore, MD 21224.Baltimore, Md, Barbados, West Indies, and Cincinnati, Ohio
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.
El texto completo de este artículo está disponible en PDF.Key words : CD14, acyloxyacyl hydroxylase, association, asthma, total IgE, soluble CD14, family-based association test
Abbreviations used : AOAH, FBAT, LD, OR, sCD14, SNP, tIgE
Esquema
| 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. Disclosure of potential conflict of interest: R. A. Mathias is employed by the Inherited Disease Research Branch, National Human Genome Research Institute, and the National Institutes of Health. The rest of the authors have declared that they have no conflict of interest. |
Vol 118 - N° 1
P. 70-77 - juillet 2006 Regresar al número
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