The -374T/A RAGE polymorphism protects against future cardiac events in nondiabetic patients with coronary artery disease.
BACKGROUND
The -374T/A polymorphism of the Receptor for Advanced Glycation End products (RAGE) may exert a protective effect toward the development of atherosclerosis. No data are currently available on the potential prognostic role of this polymorphism in patients with angiographically proven coronary artery disease (CAD). Hereto we sought to address this issue in a large consecutive cohort of patients undergoing coronary revascularization.


METHODS
A total of 643 CAD patients who underwent myocardial revascularization were followed for 4.2 years (interquartile range: 2.2-8.1 years). The rates of major cardiac adverse events (death, nonfatal myocardial infarction, and unstable angina) were compared according to the -374T/A RAGE polymorphism.


RESULTS
During a median follow-up period of 4.2 years, the study endpoint was reached by 126/643 patients (19.6%). We observed adverse cardiac events in 13.4% of patients with AA, 17.5% of those with AT, and 24.2% of those with TT genotype (p <0.05). In univariate Cox proportional hazard analysis, the AA genotype was significantly related to a better outcome in nondiabetic patients (hazard ratio: 0.47, 95% CI: 0.20-0.96; p <0.05). No association was found with adverse events in diabetic subjects. After allowance for potential confounders, the AA genotype remained a significant prognostic factor in the nondiabetic group (adjusted HR: 0.41, 95% CI: 0.17-0.94, p <0.05).


CONCLUSIONS
The -374T/A RAGE polymorphism is an independent protective factor for cardiac events in nondiabetic patients with CAD. The effect of this genetic variant seems to be attenuated in diabetics, who have chronic RAGE upregulation.
Falcone
Colomba
C
Department of Cardiology, University Hospital Fondazione IRCCS San Matteo, Pavia, Italy; Interdepartmental Center for Research in Prevention of Cardiovascular and Metabolic Disorders (CIRMC), University of Pavia, Pavia, Italy.
Geroldi
Diego
D
Buzzi
Maria P
MP
Emanuele
Enzo
E
Yilmaz
Yusuf
Y
Fontana
Jacopo M
JM
Vignali
Luigi
L
Boiocchi
Chiara
C
Sbarsi
Ilaria
I
Cuccia
Mariaclara
M
D000225:Adenine / Q000378:metabolism; D003324:Coronary Artery Disease / Q000453:epidemiology* / Q000235:genetics*; D003920:Diabetes Mellitus / Q000453:epidemiology / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005819:Genetic Markers / Q000235:genetics; D017127:Glycation End Products, Advanced / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors; D013936:Thymidine / Q000235:genetics
D005819:Genetic Markers; D017127:Glycation End Products, Advanced; D000225:Adenine; D013936:Thymidine