| Objective:To study the relationship between cytochrome oxidase CYP4502C9(CYP4502C9) gene polymorphism and patients with atrial fibrillation in kunming area for the stability of standard warfarin maintenance anticoagulation dose, so as to accord with the geng to guide the individual's warfarin drug dose for improving the using of warfarin in patients of atrial fibrillation for drug safety, efficacy and adherence,so as to the better use of warfarin anticoagulant for patients with atrial fibrillation.Methods:1-Selecting since July2010-February2012, the first affiliated hospital of kunming medicial university department of cardiology outpatient service and in hospital long-term follow-up using warfarin anticoagulant stability of the standard of90cases of patients of atrial fibrillation, all are in Kunming area. Record the patient's age, gender, height, weight, warfarin starting dose, every follow-up INR and warfarin adjustment dose. Observe the time INR was stable standard (2.0-3.0) for3months needed for; The events warfarin use of clinical follow-up:the intracranial bleeding, gastrointestinal hemorrhage, ischemic stroke, pulmonary embolism, etc.; and the genetic polymorphism influence of patients with atrial fibrillation INR was standard stable3months warfarin dose.2,All patients anticoagulant of warfarin stable enrolled standard (INR2.0-3.0) for3months, collect the peripheral blood2ml.Using the technology of PCR (polymerase chain reaction PCR), all PCR products will send to biological engineering Co., LTD, Shanghai gene sequencing, observation CYP4502C9*3-1075A/C and CYP2C9*2-430C/T gene polymorphism, according to the genotype grouping, divided into mutations group and the nonmutation group.3,Using the SPSS of17.0statistics analysis software package, count data using constitute express, measurement data using mean±standard (X±S) express, mutation and the nonmutations between the two groups is counting material used Chi-square test, measurement data is used T test, relation used Pearson related. Statistical analysis between CYP4502C9*2-430C/T and CYP4502C9*3-1075A/C gene polymorphism and anticoagulant warfarin stability of the standard dose relationship, discussing under the guidance of the genetic testing how safety, convenient and effectively using of anticoagulant warfarin treatment, improving patients with atrial fibrillation anticoagulant warfarin prevention thromboembolism compliance, effectiveness and safety.Results:(1). Sample CYP2C9*3-1075A/C and CYP2C9*2-430C/T genotype distribution which conform to the Hardy-Weinberg genetic balance law (P>0.05), indicating that the sample has representative;(2),Taking warfarin anticoagulation stable maintenance dose of90patients with af CYP4502C9*3-1075A/C gene type:find AA type for85cases (94.4%), AC type in5patients (5.6%), did not find CC type (0.00%);(3),CYP2C9*3gene its wild type*1/*1patients the average amount of warfarin maintain are higher than the type*1/*3mutations patients, its warfarin stability of maintenance dose2.58+0.51VS2.05±0.26mg/d (P=0.03P<0.05);(4),The longest follow-up time was62months, the shortest for4months, an average is8months, the observation results follow-up period of clinical events,5cases were bleeding, all for a small amount of nonfatal bleeding, mutation group bleeding is2cases (40%); The mutation bleeding group is3patients (3.5%), CYP2C9*3-1075A/C*1/*3mutations type initial phase anticoaguiation excessive and hemorrhage occurs ratio are higher than the wild type*1/*1(P=0.042P<0.05); (5),CYP2C9*2-430C/T their genotype total for the wild type all CC type, did not find the gene mutations.Conclusions:(1),Patients with atrial fibrillation in kunming region taking warfarin CYP2C9*3in genetic*1/*1for the wild type is more, its anticoagulant warfarin stable is higher than standard maintenance dose type*1/*3mutations in patients. Tip CYP2C9*3wild type in patients with warfarin metabolic faster, higher dose for warfarin, general starting dose for3mg;(2),CYP2C9*3mutations in patients with stable anticoagulant warfarin type standard, warfarin maintenance dose a wild type low, generally recommend starting dose for2mg;(3),CYP2C9*3the mutation genetic polymorphism type*1/*3anticoagulation initial phase anticoagulation excessive bleeding and ratio is higher than the wild type*1/*1of the patients; So mutations type warfarin dose should be reduced correspondingly, suggest starting dose for2mg;(4),Patients with atrial fibrillation taking warfarin in kunming region CYP2C9*2-430C/T total for the wild type, did not find the genetic mutations;(5),warfarin anticoagulation regulate using is safe and effective. |
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