Genetic Determinants of Functional Impairment in Chronic Obstructive Pulmonary Disease

the level of pulmonary artery pressure is a good indicator of prognosis in patients with COPD.The pathogenesis of PH in patients with advanced COPD is incompletely understood.Chronic hypoxemia, morphologic changes in lung parenchyma (2, 3), and inflammation (4) are potential contributing factors.Here, we investigated whether inflammatory cytokines were related to the PH process in COPD.In 50 patients with COPD (age, 62 Ϯ 3 yr), pulmonary artery pressure (Pap) was measured during right heart catheterization, and blood samples were collected for determination of genotypes and serum levels of interleukin (IL)-1␤, IL-6, and monocyte chemoattractant protein-1 (MCP-1).As compared with a control group of 50 smokers, patients with COPD had elevated serum levels of IL-6 (p Ͻ 0.001) and MCP-1 (p Ͻ 0.01) but unchanged levels of IL-1␤.Pap was positively correlated with serum IL-6 levels but not with serum IL-1␤ and MCP-1 levels.The IL-6 G/G polymorphism (-174G/C) correlated with a higher level of IL-6 among patients with COPD but not among control subjects.Patients carrying the IL6 GG genotype showed higher serum levels of IL-6 and higher Pap than those carrying the CC or CG genotype.These results indicate that the inflammatory cytokine IL-6 may contribute to PH in COPD and that IL-6 gene polymorphism confers susceptibility to PH in patients with COPD.Since we previously reported that the serotonin transporter (5-HTT) gene polymorphism was associated with PH in COPD, the combined actions of the allelic variants of these two genes are being examined in a larger population of patients with COPD.