Functional single nucleotide polymorphisms of the CCL5 gene and nonemphysematous phenotype in COPD patients.
It was previously reported that the gain-of-function -28 guanine allele of the promoter single nucleotide polymorphism (SNP; cytosine to guanine substitution of nucleotide -28 (-28C>G)) in the CC chemokine ligand 5 gene (CCL5) was associated with susceptibility to late-onset asthma in patients who developed asthma at age > or =40 yrs. The clinical diagnosis of chronic obstructive pulmonary disease (COPD) includes emphysema and small airway disease, and upregulation of CCL5 has been described in the airways of patients with COPD. It was hypothesised that CCL5 has a genetic impact upon the variable expression of emphysema in patients with COPD. Patients with COPD were studied (n = 267). All of the patients underwent pulmonary high-resolution computed tomography (CT), and visual scoring (CT score) was performed to determine emphysema severity. Three SNPs of CCL5 were genotyped, including -403G>A, -28C>G and 375T>C. A significant difference was found in CT score according to CCL5 genotype; the -28G allele was inversely associated with CT score. When the analysis was confined to 180 patients with bronchial reversibility of <15%, even stronger evidence for this association was noted. Functional single nucleotide polymorphisms in the CC chemokine ligand 5 gene were associated with milder emphysema. Together with previous findings, the present study may identify the CC chemokine ligand 5 gene as part of a common pathway in the pathogenesis of late-onset asthma and chronic obstructive pulmonary disease with milder emphysema.
Hizawa
N
N
First Dept of Medicine, Hokkaido University School of Medicine, N-15 W-7, Kita-Ku, Sapporo 060-8638, Japan.
Makita
H
H
Nasuhara
Y
Y
Hasegawa
M
M
Nagai
K
K
Ito
Y
Y
Betsuyaku
T
T
Konno
S
S
Nishimura
M
M
D000368:Aged; D000483:Alleles; D001249:Asthma / Q000235:genetics*; D018946:Chemokine CCL5 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics*; D011656:Pulmonary Emphysema / Q000235:genetics*; D012044:Regression Analysis
C483024:CCL5 protein, human; D018946:Chemokine CCL5