Functional SNPs of the CCL5 gene and non-emphysematous phenotype in patients with COPD

¹ First Dept of Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan; and Dept of Pulmonary Medicine, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan
² First Dept of Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan

^* To whom correspondence should be addressed. E-mail: ma-nishi{at}med.hokudai.ac.jp.

	Abstract

We previously reported that a gain-of-function -28G allele at the promoter SNP (-28C>G) in the CCL5 gene was associated with susceptibility to late-onset asthma in patients who developed asthma at age 40 or older. The clinical diagnosis of COPD includes emphysema and small airway disease, and upregulation of CCL5 has been described in the airways of patients with COPD. We hypothesized that the CCL5 gene has a genetic impact on the variable expression of emphysema in patients with COPD.

We studied 267 patients with COPD. All patients underwent high-resolution lung CT scans, and visual scoring (CT score) was performed to determine emphysema severity. We genotyped 3 SNPs at the CCL5 gene, including -403G>A, -28C>G, and +375T>C.

We found a significant difference in CT score according to the CCL5 genotypes; the -28G allele was inversely associated with CT score (p=0.00038). When the analysis was confined to 180 patients with bronchial reversibility less than 15%, even stronger evidence for this association was noted (p=0.00002).

Functional SNPs in the CCL5 gene were associated with milder emphysema. Together with our previous findings, our studies may identify the CCL5 gene as a common pathway in the pathogenesis of late-onset asthma and COPD with milder emphysema.