Investigating tensin1 expression and the presence of SNP identified in GWAS in COPD

Abstract

Background Chronic obstructive pulmonary disease (COPD) constitutes a major cause of morbidity and mortality. A recent genome wide association study (GWAS) showed significant association of the TNS1 gene (which encodes tensin1) with COPD. A non-synonymous single nucleotide polymorphism (SNP) (W1197R) in the TNS1 gene is associated with airflow obstruction in GWAS.

Aim To examine the mRNA, protein expression and the prevalence of W1197R of tensin1 in structural cells from healthy subjects and patients with COPD.

Methods and Materials Lung resections were immunostained for tensin1 protein expression. Cultured human airway smooth muscle cells (ASM) were evaluated for tensin1 expression using qRT-PCR and immunofluorescence. Healthy subjects and patients were genotyped using Restriction Fragment Length Polymorphism (RFLP) in ASM cells.

Results Immunohistochemical staining on lung resections (n=11) demonstrated increased tensin1 expression in the airway smooth muscle (p=0.0073) and lamina propria (p=0.0121) in COPD donors when compared to healthy controls. Expression in the apical airway epithelium was similar in both groups. A similar level of tensin1 mRNA and protein expression was detected in ASM cells, obtained from COPD donors when compared to healthy controls (n=7). RFLP revealed the presence of W1197R in healthy controls (n=7) but not in COPD donors (n=7) (p=0.0291).

Conclusion We have showed that tensin1 protein expression is increased in the lamina propria and ASM in COPD airways. Preliminary data suggest the W1197R SNP associated with COPD in GWAS is present predominantly in healthy subjects suggesting that the polymorphism is a protective factor for COPD.