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

• Respiratory Medicine

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.

Corresponding Author: Kostas Spiropoulos, MD; e-mail: spircos@upatras.gr

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