Polymorphism of the serotonin transporter gene and pulmonary hypertension in chronic obstructive pulmonary disease.
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).


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.
Eddahibi
Saadia
S
INSERM U492 and Service de Physiologie Explorations Fonctionnelles, Hôpital H. Mondor, AP-HP, 94010 Créteil, France.
Chaouat
Ari
A
Morrell
Nicholas
N
Fadel
Elie
E
Fuhrman
Claire
C
Bugnet
Anne-Sophie
AS
Dartevelle
Philippe
P
Housset
Bruno
B
Hamon
Michel
M
Weitzenblum
E
E
Adnot
Serge
S
D000328:Adult; D000368:Aged; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006965:Hyperplasia; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000235:genetics*; D000860:Hypoxia / Q000209:etiology / Q000503:physiopathology; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis / Q000235:genetics*; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D011110:Polymorphism, Genetic; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000235:genetics*; D012307:Risk Factors; D050486:Serotonin Plasma Membrane Transport Proteins; D012907:Smoking / Q000009:adverse effects; D017540:Tunica Media / Q000737:chemistry / Q000473:pathology
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins