a2b1 density and a2 polymorphisms in coronary artery disease

Abstract number: P0394

Berroeta C., Ajzenberg N., Philip I., Guillin M. C., Benessiano J.

Bichat Hospital, France

The collagen receptor a2b1 is expressed on platelets and plays a major role in platelet adhesion. A five-fold-range in a2b1 density has been reported among randomly selected individuals, and correlates with silent polymorphisms located within the coding sequence of the a2 subunit gene (807 C/T, 1648 G/A). In addition, single-base substitutions (-52 C/T and -92 C/G) within the proximal 5' regulatory region of the gene have been identified and associated to attenuated gene transcription. In vivo, differences in a2b1 platelet density could contribute to an increased risk of thrombosis or bleeding in relevant disease states. The aim of the study was to evaluate the association between coronary artery disease (CAD) and platelet polymorphisms or a2b1 density (determined by a quantitative method) and to re-examine the relation between previously described a2 polymorphisms and a2b1 density. Among 124 patients with CAD, a2b1 density was correlated with both 807 C/T and 1648 G/A (Tukey–Kramer P < 0.002). Because of linkage disequilibria between 807 C/T and 1648 G/A, three alleles have been defined: allele A1 (807 T 1648 G), allele A2 (807 C 1648 G) et al. allele A3 (807 C 1648 A). Patients A1A1 had the highest density, patients A2A2 had the lowest a2b1 density, in agreement with previous reports. Patients with allele A3 had high (A1A3) or intermediate (A2A3) a2b1 density. Study of the polymorphisms within the promoter region of the a2 gene (-52 C/T an -92 C/G) indicated a correlation between -92 G (-92 CG or GG genotypes) and low a2b1 density (Tukey–Kramer P < 0.05). However, only 4 among the 38 patients A2A2 with the lowest a2b1 density were -92 CG. These results suggest that other polymorphisms may be involved in a2a1 density variation. Comparison of CAD (n = 171) and non CAD patients (n = 96) failed to confirm the proposed association between a2 polymorphisms and CAD: platelet polymorphisms frequency and a2b1 density were similar in the two groups.