Abstract 989: Genetic Polymorphisms On The (Alpha)2 Subunit Of Platelet Integrin (Alpha)2(Beta)1 affect the release of sCD40L And P-selectin During Acute Myocardial Infarction And Increase Cardiovascular Risk
Background: Platelet membrane integrin α2β1 (I-α2β1) participates in platelet activation during the acute phase of myocardial infarction (MI), as a receptor for collagen. Platelets activation is characterized by the release of soluble CD40-ligand (sCD40L) and P-selectin (P-Sel). Although silent genetic polymorphism C807T on the α2 subunit affects the density of I-α2β1 and G1648A determines the platelet Bra/b antigen system, their role in MI is unknown. We investigated the role of C807T and A1648G on the risk for MI and the release of sCD40L and sP-sel during the acute phase of MI and one year after the event.
Methods. The study population consisted of 606 young subjects of the Caucasian race (aged 48.8±3.2 years): 219 patients with premature MI and 387 controls. A sub-population of 67 patients and 232 matched controls was recalled one year after the event for the follow-up study. Distribution of C807T and G1648A were determined by PCR, and plasma sCD40L and P-Sel by ELISA.
Results. The genotypes distribution were for 807TT/CT/CC: 34/112/73 in patients and 30/214/143 in controls (p<0.05) and for 1648GG/AG/AA: 161/50/8 in patients and 300/77/10 in controls (p=NS). The adjusted risk for MI in 807TT was 2.296(1.187– 4.440) p=0.014. During the acute phase of MI, both sCD40L and P-sel were higher in 807CT+TT (12.77±1.22pg/ml and 68.2±4.9ng/ml respectively) compared to CC (7.12±0.93pg/ml and 39.9±3.67ng/ml respectively, p<0.01 for both). One year after the event, although sCD40L and P-sel were decreased in all genotypes, they remained higher in CT+TT (8.73±0.97pg/ml and 51.1±3.6ng/ml) compared to CC(4.35±0.93pg/ml and 37.2±2.6ng/ml respectively, p<0.01 for both). In healthy controls, sCD40L and P-sel was not different in CC (4.19±0.48pg/ml and 31.1±3.1ng/ml respectively) compared to CT+TT (5.3±0.33pg/ml and 35.8±1.8 p=ns for both). G1648A had no effect on sCD40L and P-sel levels.
Conclusions. Genetic polymorphism C807T on platelet integrin α2β1 is a risk factor for premature MI, and it affects the release of sCD40L and P-selectin during the acute phase of MI, an effect sustained in the same patients one year after the event. These findings suggest that C807T polymorphism may modify platelets activation, especially during the acute phase of myocardial infarction.