RGD Reference Report - 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.

General

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.
Authors:	Ulrich, S Hersberger, M Fischler, M Nussbaumer-Ochsner, Y Treder, U Russi, EW Speich, R
Citation:	Ulrich S, etal., Respiration. 2010;79(4):288-95. Epub 2009 Jun 24.
RGD ID:	4889434
Pubmed:	PMID:19556740 (View Abstract at PubMed)
DOI:	DOI:10.1159/000226243 (Journal Full-text)
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 > or =25 mm Hg) was present in 55% and usually mild, but out of proportion (mPAP > or =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.

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
pulmonary hypertension	severity	IAGP		4889434	associated with Pulmonary Disease more ...	RGD
pulmonary hypertension	severity	ISO	SLC6A4 (Homo sapiens)	4889434; 4889434	associated with Pulmonary Disease more ...	RGD

Objects Annotated

Genes (Rattus norvegicus)

Slc6a4 (solute carrier family 6 member 4)

Genes (Mus musculus)

Slc6a4 (solute carrier family 6 (neurotransmitter transporter, serotonin), member 4)

Genes (Homo sapiens)

SLC6A4 (solute carrier family 6 member 4)

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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.