Polymorphism of the ABO gene associate with thrombosis risk in patients with paroxysmal nocturnal hemoglobinuria

Thrombosis is one of the most common causes of mortality in Paroxysmal nocturnal hemoglobinuria (PNH), but the predisposing factors for thrombosis are yet to be defined. In this study, we outline the clinical characters and the susceptible genes which lead to thrombotic formation in 104 patients with PNH. The results displayed that the genotypes with minor alleles of rs495828 or rs2519093 in the ABO gene were associated with high risk to thrombus formation (OR 5.95, 95% CI 1.90-18.65 and OR 6.3, 95% CI 2.01-19.79, respectively). Further, the TT haplotype was associated with a significant increased risk of thrombosis (OR=3.25, 95%CI 1.42-7.39). Multivariate regression analysis showed larger PNH clone and genotypes with rs495828/rs2519093 minor allele as independent risk factors for thrombosis in PNH. Some patients who came back for follow-up were tested for the plasma levels of vWF and factor VIII. Patients carrying the rs495828/rs2519093 minor allele had a significant higher level of vWF and factor VIII compared with those carrying the major allele. Therefore, we found for the first time that the rs495828/rs2519093 polymorphism represent an independent prognostic factor in PNH patients for thrombus formation, probably by increasing the vWF and factor VIII.