Different impact of deletion polymorphism of gene on the risk of renal and coronary artery disease.
OBJECTIVE
An increased frequency of the angiotensin converting enzyme (ACE) D variant has recently been reported in patients with atheromatous renal artery disease (RAD), whereas controversy exists on the risk of coronary artery disease (CAD) associated with this polymorphism. In spite of the frequent coexistence of RAD and CAD, no studies have specifically compared ACE insertion/deletion (I/D) polymorphism in patients with coronary versus renal artery disease or defined the risk of each disease associated with the D variant.


METHODS
We designed a large case-control study of subjects for whom objective renal or coronary angiographic documentation was available.


RESULTS
We analysed ACE I/D genotype and clinical-biochemical data of a total of 942 subjects (123 patients with and 137 without angiographic evidence of RAD, 420 patients with and 262 without angiographic evidence of CAD). Renal (with and without RAD) and coronary patients were similar for most conventional risk factors. There was no difference in DD frequency between CAD and CAD-free patients (38.1 versus 33.6%, NS) and DD homozygosity was not associated with CAD risk (OR = 1.27, 95% CI = 0.82-1.98). In contrast, the DD genotype was more frequent in RAD than in RAD-free patients (54.5 versus 39.4, P < 0.05) and was associated with a 2.25-fold increased risk of RAD in both the univariate and multivariate logistic regression models. Additional predictors of RAD were age and creatinine. In RAD/RAD-free patients with angiographically documented CAD, DD homozygosity was confirmed to be preferentially associated with RAD (P < 0.05).


CONCLUSIONS
ACE D variant is preferentially associated with atherosclerotic renal rather than with coronary disease, despite similar exposure to atherogenic noxae. DD homozygosity confers a 2.25-fold increased risk of RAD.
Olivieri
Oliviero
O
Department of Clinical and Experimental Medicine, Chair of Internal Medicine, University of Verona, Policlinico Borgo Roma, 37134 Verona, Italy. oliviero.olivieri@univr.it
Grazioli
Silvia
S
Pizzolo
Francesca
F
Stranieri
Chiara
C
Trabetti
Elisabetta
E
Beltrame
Federico
F
Girelli
Domenico
D
Pignatti
Pier Franco
PF
Corrocher
Roberto
R
D000367:Age Factors; D000368:Aged; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000150:complications* / Q000201:enzymology / Q000235:genetics*; D003404:Creatinine / Q000097:blood; D005260:Female; D017353:Gene Deletion; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D005919:Glomerular Filtration Rate / Q000235:genetics; D006801:Humans; D007558:Italy / Q000453:epidemiology; D007674:Kidney Diseases / Q000150:complications* / Q000201:enzymology / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D011237:Predictive Value of Tests; D012077:Renal Artery / Q000201:enzymology / Q000473:pathology*; D012307:Risk Factors
D003404:Creatinine; D007703:Peptidyl-Dipeptidase A