The Association of Monocyte Chemotactic Protein-1 and CC Chemokine Receptor 2 Gene Variants with Chronic Obstructive Pulmonary Disease

Abstract

Chemokines are potent proinflammatory cytokines that are implicated in numerous inflammatory diseases. Monocyte chemoattractant protein-1 (MCP-1) and its receptor CC chemokine receptor-2 (CCR2) play a major role in the recruitment of inflammatory cells to the lungs of patients with chronic obstructive pulmonary disease (COPD). We investigated a possible association between polymorphisms in MCP-1 and CCR2 genes (MCP-1 -2518 A/G and CCR2 190G/A or V64I) and the development of COPD. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism in 386 COPD cases and 398 age-matched healthy controls. Frequency of MCP-1 2518GG genotype for cases and controls was 0.396 and 0.324, respectively; individuals who had the GG genotype had a 1.59-fold increased risk of COPD (p=0.036). Frequency of CCR2 190AA (64I/64I) genotype for cases and controls was 0.285 and 0.21, respectively; subjects carrying the 64I/64I genotype had a 2.04-fold increased risk of COPD compared with the wild-type genotype (p=0.001). When analyzing the allele combination of these two polymorphisms, the combinations MCP-1-A/CCR2-A and MCP-1-G/CCR2-A were detected in significantly higher numbers in COPD cases than in healthy controls (odds ratio [OR]=1.50, 95% confidence interval [CI]: 1.04-2.17, p=0.032; and OR=1.89, 95% CI: 1.38-2.60, p=7.38×10(-5)). These data suggest that MCP-1 -2518 A/G and CCR2 190G/A polymorphisms are new risk factors for COPD.