Polymorphism of renin-angiotensin system genes in dialysis patients--association with cerebrovascular disease.
BACKGROUND
Polymorphisms of genes of the renin-angiotensin system (RAS) have been found in association with cerebrovascular and cardiovascular diseases in the general population. In dialysis patients, RAS gene polymorphisms have been studied in combination and separately and have yielded conflicting results.


METHODS
In this study we have analysed, in 160 dialysis patients, the distribution of the following genetic polymorphisms: M235T and T174M of the angiotensinogen gene, A1166C of the angiotensin II type 1 receptor gene and the insertion/deletion (I/D) of the ACE gene. The association of these polymorphisms with cerebrovascular and cardiovascular diseases was also tested. Healthy blood donors and hospital staff (169) were the control group for the distribution of the polymorphisms.


RESULTS
The distribution of the polymorphisms in dialysis patients as a whole did not differ significantly from that of healthy controls. However, for patients with severe cerebrovascular disease, 70% carried the D allele compared with 52% of patients without cerebrovascular disease (P=0.035). We also found that the degree of carotid artery stenosis was significantly correlated with the presence of the ACE 'D' allele in subjects on dialysis (P=0.0348).


CONCLUSIONS
The distribution of RAS genes in dialysis patients is similar to that of the normal population. The presence of the D allele of ACE gene is associated with cerebrovascular disease and the degree of carotid artery stenosis. We postulate that the ACE gene polymorphism is a risk factor for cerebrovascular disease in dialytic patients.
Losito
Attilio
A
UO Nefrologia e Dialisi, Policlinico Monteluce, Perugia, Italy and. Medical Genetics Unit, St. George's Hospital Medical School, London, UK. atlosito@tin.it
Kalidas
Kamini
K
Santoni
Stefania
S
Ceccarelli
Luigi
L
Jeffery
Steve
S
D000368:Aged; D002318:Cardiovascular Diseases / Q000453:epidemiology; D002340:Carotid Artery Diseases / Q000235:genetics / Q000503:physiopathology; D002561:Cerebrovascular Disorders / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D015995:Prevalence; D006435:Renal Dialysis; D012084:Renin-Angiotensin System / Q000235:genetics*; D012720:Severity of Illness Index