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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

69 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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