Association of defensin β-1 gene polymorphisms with asthma

Hara Levy, Benjamin A. Raby, Stephen Lake, Kelan G. Tantisira, David Kwiatkowski, Ross Lazarus, Edwin K. Silverman, Brent Richter, Walter T. Klimecki, Donata Vercelli, Fernando D. Martinez, Scott T. Weiss

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65 Scopus citations

Abstract

Background: Defensins are antimicrobial peptides that may take part in airway inflammation and hyperresponsiveness. We characterized the genetic diversity in the defensin β-1 (DEFB1) locus and tested for an association between common genetic variants and asthma diagnosis. Methods: To identify single nucleotide polymorphisms (SNPs), we resequenced this gene in 23 self-defined European Americans and 24 African Americans. To test whether DEFB1 genetic variants are associated with asthma, we genotyped 4 haplotype-tag SNPs in 517 asthmatic and 519 control samples from the Nurses' Health Study (NHS) and performed a case-control association analysis. To replicate these findings, we evaluated the DEFB1 polymorphisms in a second cohort from the Childhood Asthma Management Program. Results: Within the NHS, single SNP testing suggested an association between asthma diagnosis and a 5′ genomic SNP (g.-1816 T>C; P = .025) and intronic SNP (IVS+692 G>A; P = .054). A significant association between haplotype (Adenine, Cytosine, Thymine, Adenine [ACTA]) and asthma (P = .024) was also identified. Associations between asthma diagnosis and both DEFB1 polymorphisms were observed in Childhood Asthma Management Program, a second cohort: g.-1816 T>C and IVS+692 G>A demonstrated significant transmission distortion (P = .05 and .007, respectively). Transmission distortion was not observed in male subjects. The rare alleles (-1816C and +692A) were undertransmitted to offspring with asthma, suggesting a protective effect, contrary to the findings in the NHS cohort. Similar effects were evident at the haplotype level: ACTA was undertransmitted (P = .04) and was more prominent in female subjects (P = .007). Conclusion: Variation in DEFB1 contributes to asthma diagnosis, with apparent gender-specific effects.

Original languageEnglish (US)
Pages (from-to)252-258
Number of pages7
JournalJournal of Allergy and Clinical Immunology
Volume115
Issue number2
DOIs
StatePublished - Feb 2005

Keywords

  • Association studies
  • Asthma
  • Asthma genetics
  • Defensin

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Levy, H., Raby, B. A., Lake, S., Tantisira, K. G., Kwiatkowski, D., Lazarus, R., Silverman, E. K., Richter, B., Klimecki, W. T., Vercelli, D., Martinez, F. D., & Weiss, S. T. (2005). Association of defensin β-1 gene polymorphisms with asthma. Journal of Allergy and Clinical Immunology, 115(2), 252-258. https://doi.org/10.1016/j.jaci.2004.11.013