Endothelin-1 polymorphisms involved in impaired exercise tolerance in COPD patients. A pilot study.

INTRODUCTION Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide that may lead to impaired exercise tolerance. In this study we exhibit the relationship between two endothelin-1 (+134 3A/4A and G198T) SNPs involved in COPD and their association to impaired exercise tolerance. MATERIALS AND METHODS The study population consisted of 22 COPD smokers and 32 smoking controls which underwent pulmonary function tests to assess forced expiratory volume for 1 second (FEV1), forced vital capacity (FVC), as well as cardiopulmonary exercise testing. Single nucleotide polymorphism were isolated using Real-Time PCR. RESULTS The distribution of both genotypes (3A3A, 3A4A, 4A4A for the +134 3A/4A and GG, GT, TT for the G198T) did not different among patients and non-COPD smoking controls. Multivariate analysis showed that the 3A4A and GG genotypes in the COPD group were independently associated with better V'O2max values (Odd's Ratio (OR) = 12.5, 95% CI = -0.85-25.1, p = 0.049, and OR = 6.1, 95% CI = 0.83-11.4, p = 0.026, respectively). On the contrary analogous analysis in the non-COPD control group, showed that the 3A3A genotype was independently associated with increased V'O2/pulse (OR = 51.5, 95% CI = 17.2-85.7, p = 0.005) and the 3A4A genotype with increased DVE/DVCO2 value (OR = 3.8, 95% CI = -0.27-7.9, p = 0.054). DISCUSSION Our results show that endothelin-1 gene is implicated in exercise performance in COPD patients and might play a role in adaptation of the cardiopulmonary system to exercise.