Association between ADAMTS13 polymorphisms and risk of cardiovascular events in chronic coronary disease.
BACKGROUND
Association between ADAMTS13 levels and cardiovascular events has been described recently. However, no genetic study of ADAMTS13 in coronary patients has been described.


METHODS
Based on related populations frequencies and functional studies, we tested three ADAMTS13 polymorphisms: C1342G (Q448E), C1852G (P618A) and C2699T (A900V) in a group of 560 patients enrolled in the Medical, Angioplasty, or Surgery Study II (MASS II), a randomized trial comparing treatments for patients with coronary artery disease (CAD) and preserved left ventricular function. The incidence of the 5-year end-points of death and death from cardiac causes, myocardial infarction, refractory angina requiring revascularization and cerebrovascular accident was determined for each polymorphim's allele, genotype and haplotype. Risk was assessed with the use of logistic regression and Cox proportional-hazards model and multivariable adjustment was employed for possible confounders.


RESULTS
Clinical characteristics and received treatment of each genotype group were similar at baseline. In an adjusted model for cardiovascular risk variables, we were able to observe a significant association between ADAMTS13 900V variant and an increased risk of death (OR: 1,92 CI: 1,14-3,23, p=0,015) or death from cardiac cause (OR:2,67, CI: 1,59-4,49, p=0,0009). No association between events and ADAMTS13 Q448E or P618A was observed.


CONCLUSIONS
This first report studying the association between ADAMTS13 genotypes and cardiovascular events provides evidence for the association between ADAMTS13 900V variant and an increased risk of death in a population with multi-vessel CAD.
Heart Institute, University of São Paulo Medical School, São Paulo, Brazil.
Isolmar T
IT
Schettert
Alexandre C
AC
Pereira
Neuza H
NH
Lopes
Whady A
WA
Hueb
Jose E
JE
Krieger
D051722:ADAM Proteins / Q000235:genetics*; D000071120:ADAMTS13 Protein; D002318:Cardiovascular Diseases / Q000235:genetics*; D002908:Chronic Disease; D003327:Coronary Disease / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012306:Risk
D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human