OBJECTIVE: Platelet adhesion to the subendothelial tissue via the collagen receptor alpha2beta1 is a crucial event in vascular biology. Although evidence has been provided that the number of platelets alpha2beta1 copies is genetically determined, the molecular change primary responsible has not been yet elucidated. The aim of our present study was to investigate the effect of combined polymorphisms within both regulatory (-52C/T and -92C/G) and coding regions (807C/T and 1648A/G) of the alpha2 subunit gene on human platelets alpha2beta1 receptor density and/or susceptibility to coronary artery disease (CAD). METHODS AND RESULTS: Among 254 cardiac surgery patients, no evidence was found for an association between the alpha2 subunit gene polymorphisms and CAD. In contrast, in a subgroup of 113 patients, we observed a significant association between all polymorphisms except -52C/T and alpha2beta1 receptor level. Furthermore, when 3 groups of patients were defined according to the tertiles of platelets alpha2beta1 copies, the -92C/807T haplotype was more frequent in the group of patients with high alpha2beta1 receptor level. CONCLUSIONS: These results suggest that an individual effect of each polymorphism located either in the coding or promoter sequence of the alpha2 gene may act in combination to modulate variations in platelets alpha2beta1 receptor density.
OBJECTIVE: Platelet adhesion to the subendothelial tissue via the collagen receptor alpha2beta1 is a crucial event in vascular biology. Although evidence has been provided that the number of platelets alpha2beta1 copies is genetically determined, the molecular change primary responsible has not been yet elucidated. The aim of our present study was to investigate the effect of combined polymorphisms within both regulatory (-52C/T and -92C/G) and coding regions (807C/T and 1648A/G) of the alpha2 subunit gene on human platelets alpha2beta1 receptor density and/or susceptibility to coronary artery disease (CAD). METHODS AND RESULTS: Among 254 cardiac surgery patients, no evidence was found for an association between the alpha2 subunit gene polymorphisms and CAD. In contrast, in a subgroup of 113 patients, we observed a significant association between all polymorphisms except -52C/T and alpha2beta1 receptor level. Furthermore, when 3 groups of patients were defined according to the tertiles of platelets alpha2beta1 copies, the -92C/807T haplotype was more frequent in the group of patients with high alpha2beta1 receptor level. CONCLUSIONS: These results suggest that an individual effect of each polymorphism located either in the coding or promoter sequence of the alpha2 gene may act in combination to modulate variations in platelets alpha2beta1 receptor density.
Authors: Rehan Qayyum; Diane M Becker; Lisa R Yanek; Nauder Faraday; Dhananjay Vaidya; Rasika Mathias; Brian G Kral; Lewis C Becker Journal: Clin Transl Sci Date: 2014-07-25 Impact factor: 4.689
Authors: Marlene S Williams; Ethan J Weiss; Marc S Sabatine; Daniel I Simon; Wadie F Bahou; Lewis C Becker; Leslie V Parise; Harold L Dauerman; Patricia A French; Susan S Smyth; Richard C Becker Journal: Arterioscler Thromb Vasc Biol Date: 2010-12 Impact factor: 8.311