Association of interleukin 8 receptor alpha polymorphisms with chronic obstructive pulmonary disease and asthma

Abstract

Chronic obstructive pulmonary disease (COPD) and asthma are common complex diseases characterized by airflow obstruction and inflammatory processes in the small airways. Interleukin 8 (IL-8) is a potent pro-inflammatory cytokine which interacts with the receptors interleukin 8 receptor α (IL8RA, CXCR1) and interleukin 8 receptor β (IL8RB, CXCR2), leading to activation and migration of leukocytes. In order to evaluate the role of the IL8RA gene in the pathogenesis of COPD and asthma, we screened the coding region of IL8RA for mutations by means of single strand conformation polymorphism (SSCP) analysis in 50 probands and identified three missence mutations (M31R, S276T and R335C). Then were these three polymorphisms genotyped in 182 adult patients with COPD, 68 adult patients and 130 children with asthma and 454 healthy controls. The frequencies of the IL8RA 31R and 335C alleles were significantly increased in patients with COPD and in children with asthma compared to healthy controls (p=0,0073 and p=0,023, respectively). Thus, these polymorphisms may play a role in the pathogenesis of COPD and asthma.