Angiotensin-converting enzyme insertion/deletion polymorphism and cerebrovascular disease.
OBJECTIVE
There is evidence that an allelic variation in the angiotensin-converting enzyme (ACE) gene may confer an increased risk of vascular disease. The roles of the ACE insertion/deletion polymorphism and circulating ACE levels are unknown in cerebrovascular disease.


METHODS
We studied an insertion/deletion polymorphism within intron 16 of the ACE gene by polymerase chain reaction and plasma ACE activity in 467 cases of stroke, the pathological type of which was established by cranial CT, and 231 control subjects. ACE genotype and activity were related to stroke type and mortality at 4 weeks and 3 months.


RESULTS
No difference in genotype frequency was observed between all subjects with stroke and control subjects or between control subjects and subjects with cerebral infarction or cerebral hemorrhage. Plasma ACE activity was significantly lower in stroke patients at presentation (64.1 IU/L) than in control subjects (79.6 IU/L; P<.0001). Twenty-one patients (4.5%) with cerebral infarction died within 4 weeks and 56 patients (12%) within 3 months. These patients had significantly lower plasma ACE activity than patients who survived. There was some evidence that risk of death within 4 weeks increased with the number of D alleles (P=.02). Among survivors, plasma ACE activity showed a mean increase of 6.9 IU/L (95% confidence interval, 3.0 to 10.8) between levels at presentation and at 3 months (73.6 IU/L), the latter being similar to ACE activity in control subjects.


CONCLUSIONS
Low ACE activity at sroke presentation and possession of the D allele may be associated with increased risk of early death from acute cerebral infarction.
Catto
A
A
Diabetes and Thrombosis Research Group, Division of Medicine, University of Leeds, Leeds, UK.
Carter
A M
AM
Barrett
J H
JH
Stickland
M
M
Bamford
J
J
Davies
J A
JA
Grant
P J
PJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002423:Cause of Death; D002543:Cerebral Hemorrhage / Q000201:enzymology / Q000235:genetics; D002544:Cerebral Infarction / Q000201:enzymology / Q000235:genetics; D002561:Cerebrovascular Disorders / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000235:genetics; D016001:Confidence Intervals; D005260:Female; D017353:Gene Deletion; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors; D015996:Survival Rate; D014057:Tomography, X-Ray Computed
D007703:Peptidyl-Dipeptidase A