Increased cardiovascular risk in long-term hemodialysis patients carrying deletion allele of ACE gene polymorphism.
BACKGROUND
Controversy continues about the relation of insertion (I)/deletion (D) polymorphism of the angiotensin-converting enzyme (ACE) gene to the genetic predisposition to develop such cardiovascular diseases as myocardial infarction, stroke, and other arteriosclerotic disorders.


METHODS
To examine the relation of ACE gene polymorphism to risk for developing cardiovascular diseases in long-term hemodialysis patients, we followed up 534 patients on long-term hemodialysis therapy for 3 years after determining ACE genotype.


RESULTS
Numbers of patients with the II, ID, and DD genotypes were 208, 245, and 81, and frequencies of the I and D alleles were 0.62 and 0.38, respectively. Background characteristics, such as age, sex, causative diseases of renal failure, and preexistence of cardiovascular diseases at the time of study entry, were similar among the 3 genotype groups. Serum ACE activity was significantly greater in the DD and ID groups than the II group; however, plasma angiotensin II concentrations were not significantly different among the 3 groups. During the 3 years of follow-up, 46 fatal and 167 nonfatal cardiovascular events occurred. The incidence of these cardiovascular events was significantly associated with older age (P < 0.001), diabetes (P < 0.001), preexistence of cardiovascular diseases (P < 0.001), systolic blood pressure (P = 0.009), high cardiothoracic ratio on chest roentgenogram (P < 0.001), electrocardiographic abnormalities (P < 0.001), and low serum sodium level (P < 0.001). In addition, the incidence of cardiovascular events was greater in patients carrying the D allele (II, 22.1%; ID, 31.8%; DD, 38.3%; P = 0.010).


CONCLUSIONS
It is suggested that the D allele of ACE gene polymorphism is a risk factor for cardiovascular complications in hemodialysis patients.
Ishimitsu
Toshihiko
T
Department of Hypertension and Cardiorenal Medicine, Dokkyo University School of Medicine, Mibu, Tochigi, Japan. isimitu@dokkyomed.ac.jp
Tsukada
Kohju
K
Ohta
Satoshi
S
Inada
Hideki
H
Minami
Junichi
J
Ono
Hidehiko
H
Matsuoka
Hiroaki
H
D000368:Aged; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D011446:Prospective Studies; D006435:Renal Dialysis; D051437:Renal Insufficiency / Q000235:genetics* / Q000628:therapy*; D012307:Risk Factors
D007703:Peptidyl-Dipeptidase A