Molecular genetic analysis of antithrombin resistance for venous thromboembolism patients in central China

Objective:Antithrombin resistance is a severe type of hereditary thrombophilia newly discovered in the world,which is caused by gain-of-function mutations in the prothrombin gene.These type of mutations have been reported in 3pedigrees of Japan(p.Arg596Leu)and Serbia(p.Arg596Gln),while the existence and frequency of which still remain unclear in other parts of the world including China.We set out to investigate whether antithrombin resistance is common in the population of central China.Method:Sixty unprovoked thrombophilic patients were selected for prothrombin gene re-sequencing.Mutations p.Arg596 Leu and p.Arg596 Gln were detected using a RFLP method with HpaⅡamong the study populations,including 1 304 venous thromboembolism patients and 1 334 controls.Bioinformatics tools were employed to evaluate the consequences of identified variants.Result:Three variants(c.494CT,c.316+36GA and c.423-7GC)were identified in the 60 thrombophilic patients.Their minor allele frequencies are all higher than 0.1and they were predicted to be benign or tolerated.In contrast,the affected amino acid in p.Arg596 Leu and p.Arg596 Gln reported previously were highly conserved among various species.However,the two mutations were not observed in the study population.Conclusion:p.Arg596 Leu and p.Arg596 Gln may be very rare and antithrombin resistance is not a common risk factor for inherited thrombophilia in central China.