Polymorphisms in genes of the renin-angiotensin system and cerebral small vessel disease.
BACKGROUND
Genetic variation in the renin-angiotensin system (RAS) has been implicated in stroke, particularly the small vessel disease (SVD) subtype. Furthermore, there may be two distinct subtypes of cerebral SVD, isolated lacunar infarction (ILI) and ischaemic leukoaraiosis (ILA).


METHODS
300 patients with well-phenotyped SVD and 600 controls were genotyped for five polymorphisms in the angiotensinogen (AGT) gene and eight polymorphisms within the angiotensin-converting enzyme (ACE) gene.


RESULTS
AGT and ACE polymorphisms and haplotypes were no more common in SVD cases as a whole or the two subtypes. Amongst hypertensives only, an AGT promoter polymorphism (-20A-->C), was associated with the ILA subtype (multivariate odds ratio 1.716, 95% confidence interval 1.073-2.746, p = 0.024).


CONCLUSIONS
RAS genetic variants are not strong risk factors for cerebral SVD. The AGT -20C allele may be a risk factor for the leukoaraiosis subtype amongst hypertensives.
Gormley
K
K
Centre for Clinical Neuroscience, St. George's University of London, London, UK.
Bevan
S
S
Markus
H S
HS
D000808:Angiotensinogen / Q000235:genetics; D001808:Blood Vessels / Q000473:pathology; D001921:Brain / Q000098:blood supply*; D020520:Brain Infarction / Q000235:genetics; D002545:Brain Ischemia / Q000235:genetics; D016022:Case-Control Studies; D002561:Cerebrovascular Disorders / Q000235:genetics* / Q000473:pathology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D006973:Hypertension / Q000150:complications; D049292:Leukoaraiosis / Q000235:genetics; D015810:Linkage Disequilibrium; D016015:Logistic Models; D016017:Odds Ratio; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012084:Renin-Angiotensin System / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D006113:United Kingdom
D000808:Angiotensinogen; D007703:Peptidyl-Dipeptidase A