Genetic variants of the gasdermin B gene associated with the development of aspirin-exacerbated respiratory diseases

Background:

Aspirin-exacerbated respiratory disease (AERD) is characterized by a severe and sudden asthma attack after aspirin ingestion in patients with asthma. We studied associations with six common single nucleotide polymorphisms (SNP) of the gasdermin B gene (GSDMB).

Objective:

DNA obtained from 572 patients with asthma (with AERD, n = 165; and with aspirin-tolerant asthma, n = 407) and 391 normal controls was subjected to genotyping of six SNPs of GSDMB.

Methods:

An association analysis between GSDMB variants and AERD, with a fall rate of the forced expiratory volume in the first second of expiration (FEV₁), was performed by using logistic and regression models.

Results:

Two SNPs in the intron (rs870830, rs7216389) showed significant associations with AERD (minimum p = 7.00 × 10⁻⁴ in the dominant model), even after Bonferroni correction (p_corr = 0.01 for the rs870830). Regression analysis of the genetic variants with FEV₁ revealed significant associations with rs870830 and the haplotype 2 (p_corr = 4.71 × 10⁻⁴ for rs870830 and p_corr = 1.14 × 10⁻³ for haplotype 2, respectively).

Conclusion:

We found strong associations among GSDMB polymorphisms and the presence of AERD and FEV₁ in Korean patients with asthma. Our findings indicated that genetic variations of GSDMB may be associated with the development of AERD and aspirin-induced bronchospasm.