Angiotensin-converting enzyme gene polymorphisms and prognosis in chronic thromboembolic pulmonary hypertension.
BACKGROUND
Angiotensin-converting enzyme (ACE) plays an important role in vascular remodeling in pulmonary hypertension, and ACE gene polymorphism is associated with exercise-induced pulmonary hypertension in Japanese patients with chronic obstructive pulmonary disease. The present study was designed to investigate if ACE-insertion (I)/deletion (D) polymorphism might be related to the susceptibility, severity, and disease outcome in chronic thromboembolic pulmonary hypertension (CTEPH).


RESULTS
ACE-I/D genotypes were determined in 95 consecutive CTEPH patients (46 underwent surgery, 49 received medical treatment) and 97 controls. The frequencies of genotypes and alleles were not significantly different between patients and controls. Clinical characteristics were compared among ACE genotypes (II, ID, DD). ACE D allele carrier (ID plus DD) was associated with a lower 6-min walk test distance compared with D allele non-carrier (II) (330+/-102 (mean +/- SD) vs 381 +/-85 m, p=0.046). Kaplan-Meier analysis in the medically treated group showed significantly deteriorated survival for D allele carriers compared with D allele non-carriers (p=0.0389). Multivariate analysis revealed that age (p=0.013), pulmonary vascular resistance (p=0.008), and D allele carrier status (p=0.021) were independent predictors of survival.


CONCLUSIONS
ACE D allele carrier is possibly one of the prognostic factors for medically treated CTEPH patients.
Tanabe
Nobuhiro
N
Department of Respirology, Graduate School of Medicine, Chiba University, Japan. ntanabe@faculty.chiba-u.jp
Amano
Shinya
S
Tatsumi
Koichiro
K
Kominami
Satoshi
S
Igarashi
Natsuhiko
N
Shimura
Ryuhi
R
Matsubara
Hiroshi
H
Kasahara
Yasunori
Y
Takiguchi
Yuichi
Y
Kuriyama
Takayuki
T
D000328:Adult; D000483:Alleles; D044466:Asian People; D002908:Chronic Disease; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D011379:Prognosis; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000235:genetics; D011655:Pulmonary Embolism / Q000209:etiology / Q000235:genetics*; D012307:Risk Factors
C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A