Severe pulmonary hypertension is uncommon in patients with COPD. When it occurs, another cause must be sought. COPD with severe pulmonary hypertension and no other possible cause shares features with pulmonary vascular diseases, such as idiopathic pulmonary hypertension.

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 (nϭ67) and the UK (nϭ36), 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 34Ϯ3, 23Ϯ1, and 22Ϯ2 mm Hg (meanϮSEM), respectively (PϽ0.01). Corresponding systolic PAP values in the UK were 40Ϯ3, 28Ϯ3, and 24Ϯ3 mm Hg, respectively (PϽ0.01). 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

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