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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:1756.)
© 2005 American Heart Association, Inc.

Thrombosis

Association of the –92C/G and 807C/T Polymorphisms of the ₂ Subunit Gene With Human Platelets ₂ß₁ Receptor Density

Nadine Ajzenberg; Clarisse Berroeta; Ivan Philip; Bernard Grandchamp; Pierre Ducellier; Virginie Huart; Patrice Verpillat; Marie-Claude Guillin; Joelle Benessiano

From the Departments of Hematology (N.A., P.D., M.-C.G.), Anesthesiology (C.B., I.P.), and Biochemistry (B.G.), the Clinical Investigation Center (V.H.), Biostatistics (P.V.), Hopital Bichat, Assistance Publique-Hopitaux de Paris, and INSERM U698 (N.A., C.B., M.-C.G., J.B.), Hopital Bichat, University Paris, France.

Correspondence to Dr N. Ajzenberg, Service d’Hématologie et Immunologie, Hôpital Bichat, 46 rue Henri Huchard, 75018, Paris, France. E-mail nadine.ajzenberg{at}bch.ap-hop-paris.fr

Objective— Platelet adhesion to the subendothelial tissue via the collagen receptor ₂ß₁ is a crucial event in vascular biology. Although evidence has been provided that the number of platelets ₂ß₁ 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 ₂ subunit gene on human platelets ₂ß₁ 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 ₂ 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 ₂ß₁ receptor level. Furthermore, when 3 groups of patients were defined according to the tertiles of platelets ₂ß₁ copies, the –92C/807T haplotype was more frequent in the group of patients with high ₂ß₁ receptor level.

Conclusion— These results suggest that an individual effect of each polymorphism located either in the coding or promoter sequence of the ₂ gene may act in combination to modulate variations in platelets ₂ß₁ receptor density.

An important combined effect of the –92C and 807T polymorphisms of the ₂ gene in increasing the expression of human platelet ₂ß₁ receptors has been observed, suggesting that this haplotype could modulate variations in ₂ß₁ receptor density.

Key Words: –92C/G • 807C/T polymorphism • ₂ß₁ density

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