Study Of CYP2C9 & VOKRC1 Gene Polymorphisms And Their Individual Significance On Warfarin Anticoagulant Doses

BackgroundWarfarin is a coumarin anticoagulants.Warfarin is usually used in the treatment of blood clots,such as deep vein thrombosis and pulmonary embolism,preventing stroke in atrial fibrillation,or artificial heart valve disease after heart valve replacement.Warfarin has been preferred as anticoagulants in clinic.Long treatment times and large differences between patients and warfarin can cause a lot of risk,such as bleeding and thrombosis.Because of individual difference is relatively large,so individualized treatment plan is more practical value.In recent years,through the further understanding of drug metabolism,it was found that some genes polymorphism affects drug metabolism effect,this can be used as one reason for the difference between the individual warfarin uses.Warfarin is a mixture of consists of two parts.One is S-warfarin,S-warfarin metabolism by CYP2C9,so CYP2C9 to warfarin metabolism has a very important role.The other part is R-warfarin,R-warfarin is metabolismed by CYP3A4,CYP1A2,CYP1A1 and CYP2C19.S-warfarin cause effect 3-5 times than that of R-warfarin.About the clinical effect of warfarin,vitamin K epoxide reductase complex under the action of warfarin was converted into hydroquinone.And VKORC1 can do to prevent clotting factor ?,?,?,C and S into the X and anticoagulation are the process of active matter.So the research of CYP2C9 and VKORC1 gene polymorphism have guiding significance for warfarin.Objective1.Discusses P4502C9 cytochrome oxidase(CYP2C9)gene polymorphism;and the correlation between different genotypes and warfarin.2,explore vitamin K epoxide reductase complex 1(VKORC1)gene polymorphism without gene distribution and the correlation between warfarin;3,observation of age,gender,height,weight,type of CYP2C9 and VKORC1 gene and other relations with warfarin stable period.Materials and MethodsCollected since April 2015 to June 2016 in our line of heart valve replacement surgery patients,After admission the patient was given an empty abdominal blood,and the CYP2C9 and VKORC1 genotype were measured,screening cases according to inclusion criteria and exclusion criteria.Concurrent registration and follow-up,record the object of study the following information:1.case collection patients' gender,age,height,weight,operation method,type of CYP2C9 and VKORC1 gene;2,follow-up of patients with warfarin doses,PT and PT INR value,special medicine,atrial fibrillation,do you have any bleeding and thrombosis;3,postoperative anticoagulation related:including postoperative anticoagulation drug varieties,dosage,taking other drugs at the same time;4,the operation information:anesthesia and operation method,etc.Results1,65 cases for samples,CYP2C9 pure and the AA genotype of wild type 51 cases(79%heterozygous mutation type AC 14 cases(21%),homozygous mutant did not find the CC type(0.0%);VKORC1-1639-A/G genotype,found that the wild.type AA 56 cases(86%),heterozygous mutation GA type 9 cases(14%),and found no homozygous mutant GG type(0.0%);2,for warfarin dose comparison between different gender,the results show that in 65 patients taking warfarin for 31 cases of men,men taking warfarin(x =3.60 mg,S = 1.07);Women for 34 cases,men taking warfarin dose variance respectively:(x = 2.94 mg,S = 1.13),on gender warfarin dose compared between groups,the homogeneity of variance after inspection,so the strict two independent t test were analyzed,and the results show that the male warfarin dose more than women,but there was no statistically significant difference between the group(t = 2.406,P = 2.406).3,for comparison between different CYP2C9 warfarin dose,the results show that 65 cases of patients taking warfarin,the CC/AA genotype 51 cases,the CC/AA genotype taking warfarin dose of mean and variance are:(x = 3.43,S = 1.13);Including 14 cases of CC/AC genotype CC/AC genotype taking warfarin dose of mean and variance are:(x =2.63,S = 1.00).On warfarin dose groups compared between CYP2C9,after homogeneity of variance test,so the strict two independent t test were analyzed,and the results show that the CC/AA type warfarin dose is greater than the CC/AC type,and the differences between groups was statistically significant(t = 2.381,P = 2.381).4,for 65 cases of VKORC1 testing samples,warfarin dose differences between different genotypes,there are 56 cases is AA genotype.AA genotype taking warfarin dose of mean and variance,respectively:(x = 3.01,S = 0.94);Including 9 cases of AG genotype and AG genotype taking warfarin dose of mean and variance are:x = 4.46,S = 1.34;Between VKORC1 warfarin dose compared between groups,the homogeneity of variance after inspection,so the strict two independent t test were analyzed,and the results show that GA warfarin dose is greater than the AA sex,sex and group was statistically significant difference between(t = 4.021,P = 4.021).Conclusions1,the different between patients with CYP2C9 gene polymorphism with warfarin use oral dose difference.Genotypes of CYP2C9(AC)of warfarin use and genotype of CYP2C9 compared(AA)has obvious difference,the former dosage is significantly higher than the latter.Dose difference significantly between groups,statistically significant;2 and the influencing factors of Shandong ethnic Han warfarin dosage has a lot of,including VKORC1 gene polymorphism is one of the important influencing factors.Genotype of VKORC1-1639 of warfarin use in(AA)and genotype of VKORC1-1639(GA)has obvious difference,the former dosage is significantly lower than the latter,and dose differs significantly between each group,with statistical difference;Warfarin doses has 3,gender differences,there are statistically significant(P<0.05),and the male warfarin doses than women warfarin doses;Warfarin doses have differences between weight was statistically significant(P<0.05),increased with the increase of weight warfarin doses;In terms of age over 60 years of age,50 to 60 years old,and there are differences between people under 50 but without statistical significance;4,there were significant positive correlation between height and warfarin dose(r =0.309,P = 0.309),with the growth of height,namely warfarin dose as also increase;Significant positive correlation between weight and warfarin dose(r = 0.412,P = 0.001)with the increase of body weight,warfarin dose as also increase;here is significant correlation between gender and warfarin dose(r = 2.90,P = 2.90).And results show that between age and warfarin dose has not yet found significant correlation.