Association of defensin β-1 gene polymorphisms with asthma - 18/08/11
, Benjamin A. Raby, MD b, Stephen Lake, ScD b, Kelan G. Tantisira, MD b, David Kwiatkowski, MD, PhD b, d, e, Ross Lazarus, MD b, Edwin K. Silverman, MD, PhD b, Brent Richter, MS b, Walter T. Klimecki, MD c, Donata Vercelli, MD c, Fernando D. Martinez, MD c, Scott T. Weiss, MD, MS b, d
Reprint requests: Hara Levy, MD, Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115.Boston, Mass, and Tucson, Ariz
Abstract |
Background |
Defensins are antimicrobial peptides that may take part in airway inflammation and hyperresponsiveness.
Objective |
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.
Le texte complet de cet article est disponible en PDF.Key words : Asthma, asthma genetics, defensin, association studies
Abbreviations used : ACTA, CAMP, CF, COPD, DEFB1, FBAT, htSNP, HWE, NHS, SNP, UTR
Plan
| CAMP was supported by contracts N01-HR-16044, 16045, 16046, 16047, 16048, 16049, 16050, 16051, and 16052 from the National Heart, Lung and Blood Institute. The CAMP Genetics Ancillary Study was supported by P01 HL67664 (Dr Weiss) from the National Heart, Lung and Blood Institute. In addition, this work was supported by research grants and contracts K23HL074202-01 (Dr Levy) and 1 U01 HL66795 21 (Dr Weiss) from the National Heart, Lung and Blood Institute. |
Vol 115 - N° 2
P. 252-258 - février 2005 Retour au numéro
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