Biochemical activity and gene analysis of inherited protein C and antithrombin deficiency in two Chinese pedigrees

Background We identified the gene mutations in two Chinese pedigree of type Ⅰ hereditary protein C deficiency and type Ⅰ hereditary antithrombin deficiency.Methods The plasma level of protein C activity (PC∶A),protein C antigen (PC∶Ag),protein S activity,antithrombin activity (AT∶A) and antithrombin antigen (AT∶Ag) of propositi and two family members were detected using ELISA and chromogenic assay,respectively. All exons and intron-exon boundaries of protein C gene and antithrombin gene were analyzed by direct sequencing of the corresponding amplified PCR products in DNA from the propositus. Results The plasma PC∶A and PC∶Ag of propositus 1 was 26% and 1.43 mg/dl,respectively. The PC∶Ag and PC∶A of his father were normal. The decreased PC∶A level was seen in his mother and 4 of his maternal pedigree. PS∶A and AT∶A were all normal in pedigree 1 members. A C5498T heterozygous mutation in exon 3 of protein C gene,resulting in the substitution of Arg for Trp at the 15th amino acid,was identified in propositus 1 and 8 of his relatives. The plasma AT∶A and AT∶Ag of propositus 2 was 48.6% and 10.4 mg/dl,respectively. The reduced AT∶A and AT∶Ag levels were found in his father and 5 of paternal pedigree. PC∶A,PC∶Ag and PS∶A were all in normal range. A heterozygous 13387-9G deletion in exon 6 of antithrombin gene was identified in propositus 2. This mutation introduced a frameshift and a premature stop at codon 426 and existed in 6 members of pedigree 2.Conclusion The C5498T heterozygous mutation in exon 3 of protein C gene,first reported in China,leads to type I hereditary protein C deficiency. The 13387-9G deletion,a novel mutation,can cause antithrombin deficiency and thrombosis.

A Randomized Controlled Trial of Adjunctive Bunchang Naoxintong Capsule (步长脑心通胶囊) Versus Maintenance Dose Clopidogrel in Patients with CYP2C19*2 Polymorphism

Objective：To determine the impact of adjunctive Buchang Naoxintong Capsule（步心脑心通胶囊,NXT） on dual antiplatelet therapy in patients with cytochrome P450 2C19＊2（CYP2C19＊2） polymorphism undergoing percutaneous coronary intervention（PCI）.Methods：Ninety patients with CYP2C19＊2 polymorphism were enrolled,and their genotypes were confirmed by polymerase chain reaction（PCR）.The patients were randomly assigned to receive either adjunctive NXT（triple group,45 cases） or dual antiplatelet therapy（dual group,45 cases） using a computer-generated randomization sequence and sealed envelopes.Platelet function was assessed at baseline and 7 days after treatment with conventional aggregometry.Subsequent major adverse cardiovascular events（MACE,including sudden cardiac arrest and acute coronary syndrome） were recorded during a 12-month followup.Results：Baseline platelet function measurements were similar in both groups.After 7 days,percent inhibitions of maximum platelet aggregation and late platelet aggregation were significantly greater in the triple versus dual group（42.3%±16.0%vs.20.8%±15.2%,P〈0.01,and 54.7%±18.3%vs.21.5%±29.2%,P〈0.01,respectively）.During the 12-month follow-up,the rate of subsequent MACE（6/45） was significantly lower in the triple group compared with the dual group（14/45;P〈0.05）.Conclusion：Adjunctive NXT to maintenance dose clopidogrel（75 g） could enhance the antiplatelet effect and decrease subsequent MACE in patients with the CYP2C19＇2polymorphism undergoing PCI.