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Updated: Jul 23, 2026

Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry
Published on: June 21, 2018
Association of defensin beta-1 gene polymorphisms with asthma
Hara Levy1, Benjamin A Raby, Stephen Lake
1Children's Hospital, Division of Pulmonary Medicine, Boston, MA, USA. Hara.levy@childrens.harvard.edu
Background:
Defensins are antimicrobial peptides that may take part in airway inflammation and hyperresponsiveness.
Objective:
We characterized the genetic diversity in the defensin beta-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.
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