The Pl(A2) polymorphism of the platelet glycoprotein IIIA gene as a risk factor for acute renal allograft rejection

Glycoprotein IIIa/IIb is a membrane receptor for fibrinogen and von Willebr and factor that plays an important role in platelet aggregation. The beta i ntegrin chain of this receptor, GPIIIa, is polymorphic, and the allele know n as Pl(A2) has been associated with coronary thrombosis. The GPIIIa genoty pe of a cohort of 119 consecutive renal allograft recipients (46.3 +/- 13 y r; 85 M/34 F; 24.4% diabetic patients) was determined by PCR-restriction fr agment length polymorphism, and those patients were followed for at least 1 2 mo. From 119 patients with at least 1 yr of follow-up, those who suffered an acute rejection (n = 52) showed a lower proportion of HLA-DR beta 1 ide ntity with the donor (7.7% versus 23.9%; P = 0.03), a higher proportion of cytomegalovirus-positive (CMV+) donors/CMV- recipients (21% versus 7.5%; P = 0.05), and the Pl(A2) allele was more frequent (38.1% versus 26.9%; P = 0 .02) compared with patients free of acute rejection (n = 67). No other vari able was associated with acute rejection in the univariate analysis. The im pact of the three above-mentioned significant variables on acute rejection was analyzed by stepwise logistic regression. The presence of the Pl(A2) al lele yielded an odds ratio of 2.75 (95% confidence interval, 1.01 to 7.93) and an HLA-DR pi identity of 0.2 (95% confidence interval, 0.06 to 0.99) fo r suffering an acute rejection episode. In addition, the serum creatinine a t discharge was higher in Pl(A2)-positive versus Pl(A2)-negative patients ( 2.2 +/- 1.6 versus 1.5 +/- 0.6 mg/dl, respectively; P = 0.01), and the prev alence of proteinuria >1.5 g/d 1 yr after transplantation was significantly higher among patients showing the plA2 allele (16% versus 3%; P = 0.02). F inally, in the entire cohort of patients, the 2-yr graft survival was signi ficantly lower in Pl(A2)-postitive (n = 33) compared with Pl(A2)-negative ( n = 76) patients (85.7% versus 97.2%; P = 0.015). No differences were found in patient survival (95.2% versus 98.7%, respectively). Proportional hazar ds regression analysis (Cox regression model) confirmed that serum creatini ne level at discharge is the best predictor of allograft survival, followed by CMV status, delayed graft function, and the glycoprotein IIIa/IIb genot ype. The Pl(A2) Polymorphism is an independent risk factor for acute renal graft rejection, affecting short-term graft survival. Future studies aimed at preventing the hemostatic imbalance favoring platelet aggregation associ ated with this polymorphism may be important in preventing acute rejection and its impact on chronic rejection.