Association of IL-13 gene polymorphisms with airway hyperresponsiveness in a Japanese adult asthmatic population

Abstract

Background: A single nucleotide polymorphism (SNP; rs20541) in the IL-13 gene has been recognized as a risk factor for asthma. This SNP causes Arg to Gln (Q) substitution at position 110 in the mature IL-13 protein. We have recently showed that FEV1 in asthmatics with the Q110 variant of IL-13 declined faster, and progressive airway remodeling was observed in these subjects (Wynn, 2003 [1]). However, the effects of the IL-13 variant on airway hyperresponsiveness (AHR) remain to be elucidated. We analyzed the relationship between SNP rs20541 in IL-13 and AHR in asthmatics.

Methods: We recruited 182 asthmatics who visited the asthma outpatient clinic at Iwate Medical University Hospital from 2006 to 2011. Subjects were genotyped for rs20541. Asthma severity, atopic status, age of asthma onset, serum IgE concentration, AHR, and pulmonary function were studied in these subjects. AHR was measured using the continuous methacholine inhalation method (Astograph; Chest; Tokyo, Japan).

Results: Genotyping of rs20541 revealed 26 A/A, 77 A/G, and 79 G/G patient genotypes. The D min (U) of the 3 genotypes was 1.17±0.300 in A/A, 1.99±0.35 in A/G, and 2.85±0.39 in G/G. The D min in the 3 genotypes was significantly different. Spirometric data revealed that % FEV1 and % FEF75 were significantly different among the 3 groups of IL-13 genotypes, whereas no significant differences were observed in therapeutic steps, atopic status, house dust mite sensitization, or serum IgE concentration.

Conclusion: The SNP rs20541 in IL-13 was associated with AHR in Japanese adult asthmatics.

Keywords: % FEV(1); % FVC; % VC; AHR; ANOVA; ASM; Airway hyperresponsiveness; Atopic status; BAL; FEF(25–75)%; FEF(50)% and FEF(75)%; FEV in 1s/FVC; FEV(1); FEV(1)/FVC; FVC; GM-CSF; HDM; ICS; IL-13; Polymorphism; Q110; Rrs; SNP; VC; airway hyperresponsiveness; airway smooth muscle; analysis of variance; bronchoalveolar lavage; forced expiratory flow when 50% and 75% of the FVC has been exhaled, FEF(75)%; forced expiratory volume in 1s; forced vital capacity; granulocyte-macrophage colony-stimulating factor; house dust mite; inhaled corticosteroid; mean forced expiratory flow during the middle half of the FVC; respiratory resistance; single nucleotide polymorphism; the percentage of FEV in 1s; the percentage of FVC; the percentage of VC; the substitution of Arg (R) with Gln (Q) at position 110 in the mature IL-13 protein; vital capacity.