on October 6, 2003
Published online before print October 6, 2003, doi: 10.1161/01.CIR.0000091409.53101.E8
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Submitted on February 7, 2003
From INSERM U492 and Service de Physiologie Explorations Fonctionnelles, Hôpital H. Mondor, Créteil (S.E., S.A.); Service de Pneumologie, Hôpital de Hautepierre, Strasbourg (A.C., A.-S.B., E.W.); Service de Chirurgie Thoracique, Hôpital Marie Lannelongue, Le Plessis Robinson (E.F., P.D.); Service de Pneumologie, Hôpital Intercommunal de Créteil, Créteil (C.F., B.H.); and INSERM U288, Faculté de Médecine Pitié-Salpêtrière, Paris (M.H.), France; and Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, UK (N.M.). * To whom correspondence should be addressed. E-mail: serge.adnot{at}creteil.inserm.fr.
Background--The serotonin transporter (5-HTT) is involved in the pulmonary artery smooth muscle hyperplasia that leads to pulmonary hypertension (PH). Because hypoxia and 5-HTT gene polymorphism control 5-HTT expression, we examined 5-HTT gene polymorphism and PH in hypoxemic patients with advanced chronic obstructive pulmonary disease (COPD). Methods and Results--In 103 patients with COPD recruited in France (n=67) and the UK (n=36), we determined 5-HTT gene polymorphism and pulmonary artery pressure (PAP) measured during right heart catheterization (France) or Doppler echocardiography (UK). Ninety-eight subjects from the 2 countries served as control subjects. The distribution of 5-HTT gene polymorphism did not differ between patients and control subjects. In patients carrying the LL genotype, which is associated with higher levels of 5-HTT expression in pulmonary artery smooth muscle cells than the LS and SS genotypes, PH was more severe than in LS or SS patients. Mean PAP values in patients from France with the LL, LS, and SS genotypes were 34±3, 23±1, and 22±2 mm Hg (mean±SEM), respectively (P<0.01). Corresponding systolic PAP values in the UK were 40±3, 28±3, and 24±3 mm Hg, respectively (P<0.01). Compared with control subjects, platelet 5-HTT protein was increased in COPD patients in proportion to the hypoxemia level, and strong 5-HTT immunostaining was observed in remodeled pulmonary arteries from COPD patients. Conclusions--5-HTT gene polymorphism appears to determine the severity of PH in hypoxemic patients with COPD. Because PH is an important prognostic factor in this disease, recognition of patients at risk for PH should be helpful in managing COPD.
Revised on July 22, 2003
Accepted on July 23, 2003
Polymorphism of the Serotonin Transporter Gene and Pulmonary Hypertension in Chronic Obstructive Pulmonary Disease
Saadia Eddahibi PhD,
Key words: chronic pulmonary disease • pulmonary hypertension • genes
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