Clinical Investigations

Genetic Polymorphisms of the Serotonin Transporter, but Not the 2a Receptor or Nitric Oxide Synthetase, Are Associated with Pulmonary Hypertension in Chronic Obstructive Pulmonary Disease
Silvia Ulrich, Martin Hersberger, Manuel Fischler, Yvonne Nussbaumer-Ochsner, Ursula Treder, Erich W. Russi, Rudolf Speich

Clinics of Internal Medicine and Pulmonology, University Hospital Zürich, Zürich, Switzerland

Address of Corresponding Author

Respiration 2010;79:288-295 (DOI: 10.1159/000226243)

  Key Words

• Chronic obstructive pulmonary disease
• Genetic
• Polymorphism
• Pulmonary hypertension
• Serotonin
• Serotonin transporter

  Abstract

Background: Pulmonary hypertension (PH) is prognosti- cally important in chronic obstructive pulmonary disease (COPD). Since PH only weakly correlates with hypoxemia, other factors must play a role. Objective: To investigate whether polymorphisms of the serotonin transporter (5HTT), serotonin-2a receptor (5HTR2a) and endothelial nitric oxide synthetase (eNOS) are related to PH in COPD. Methods: In 59 COPD patients who underwent right heart catheterization, 6-min walking distance, NYHA functional class, pulmonary function tests, blood gases and 5HTT, 5HTR2a and eNOS (4ab and T298C) polymorphisms were determined. Results: Forty-nine COPD patients in NYHA functional class III–IV were included. Ten were excluded due to comorbid causes of PH (mainly chronic thromboembolic). PH (mPAP ≧25 mm Hg) was present in 55% and usually mild, but out of proportion (mPAP ≧40 mm Hg) in 12%. Patients with PH had significantly higher frequencies of the 5HTT-L-allele (52%) compared to individuals without PH (36%), and LL homozygote patients had more severe PH. In patients with out-of-proportion PH, the L-allelic frequency was even 75%. We found no association of 5HTR2a and eNOS polymorphism with PH in COPD. Conclusions: In this COPD cohort we confirm that PH is frequent and usually mild, but out of proportion in a subgroup. We found a significant association of the L-allelic variant of 5HTT with PH overall and especially in out-of-proportion PH. These findings may point towards a role of the serotonin system in COPD-PH and warrant further studies.

Copyright © 2009 S. Karger AG, Basel

  Author Contacts

Silvia Ulrich, MD
Internal Medicine Clinic, University Hospital Zürich
Rämistrasse 100
CH–8091 Zürich (Switzerland)
Tel. +41 44 255 43 62, Fax +41 44 255 44 15, E-Mail silvia.ulrich@usz.ch

  Article Information

Received: January 14, 2009
Accepted after revision: April 11, 2009
Published online: June 24, 2009
Number of Print Pages : 8
Number of Figures : 3, Number of Tables : 4, Number of References : 40