| Objective：To study the gene polymorphism of cytochrome P4502C9(CYP2C9) andvitamin K epoxide reductase complex subunit1(VKORC1) to patients who suffered lowerextremity deep vein thrombosis (LEDVT), combining some relevant non-genetic factorsabout the application dosage of warfarin to establish a daily maintenance dose algorithm ofwarfarin for the patients who will suffer LEDVT.Methods：From Nov2012to Feb2013,40LEDVT patients were enrolled to ourresearch who come from the ward and inpatient of department of interventional treatmentof the first affiliated hospital of Soochow university and the ward of department ofvascular and interventional treatment of the Soochow municipal hospital. All of aboveeligible patients’ diagnosis of LEDVT were confirmed by the lower limb venous Doppleror lower limb anterograde venography and their international normalized ratio (INR)reached the range of2.0~3.0for three consecutive times. Age, gender, body weight,height and the dosage of daily maintenance warfain were recorded as patients’characteristic.2ml peripheral venous blood for each LEDVT patient was taken and then itwere send to the department of clinical pharmacology research laboratory of the firstaffiliated hospital of Soochow university to detect CYP2C9-1075andVKORC1-1639A>G polymorphisms with allele specific PCR technology combine withProbe method. Using SPSS17.0statistical software for statistical processing, with patientsage, gender, body weight, height, CYP2C9-1075and VKORC1-1639A>G for variables,trying to establish a suitable maintenance dose algorithm of warfarin for LEDVT throughmultivariate linear regression analysis.Results：①.Genotypes of VKORC1-1639A> G in warfarin using in the LEDVTpatients found two genotypes: homozygote-1639AA, heterogote-1639AG. Type AA werefound in36cases (90%), type AG were found in4(10%).The frequency of A and G allele were95%,5%respectively. There were two alleles(*1、*3) and two genotypes (*1*1、*1*3)at gene locus CYP2C9-1075.Genoptype*1*1were found in39cases (97.5%) andgenotypes*1*3were found in1case (2.5%).The frequencies of*1and*3allele are98.75%,1.25%respectively.②.There were no statistical significance（P>0.05）in age,height, body weight between different genotypes, such as between genotype AA and AG,*1/*1and*1/*3.③. Without considering the affects of CYP2C9gene polymorphism, thedaily warfarin maintenance dose of genotype AG increased by47%（4.63±0.93vs3.13±0.95）compared to the dose of genotype AG. Without considering theaffects of VKORC1gene polymorphism, the daily warfarin maintenance dose of genotype*1/*3decreased by24%（3.29±1.05vs2.50） compared to the dose ofgenotype*1/*1.④. Different combination of VKORC1andCYP2C9genotypes in LEDVTpatients required daily warfarin maintenance dose as following:Genotype of AG+*1/*1inpatients required daily warfarin maintenance dose increased by85.2%（4.63±0.96vs2.50,p=0.022）than those patients with genotype ofAA+*1/*3.⑤.The singlefactor associated to warfarin maintenance dosage regression analysis revealed age, bodyweight and VKORC1-1639A> G would contributes to10.5%,21.6%, and19%to theindividual differences of warfarin maintenance dosage, respectively. However, thevariables contain gender, height and CYP2C9-1075have no impact to the dosage ofwarfarin maintenance.⑥.Enrolling mentioned above six variables as independent variableand the daily dose of warfarin as dependent variable, a warfarin maintenance dosealgorithm was established as following: Dose（mg）=-0.539+0.037x Weight+1.171xVKORC1, this model could explain about32.5%individual dose requirement.Conclusion：Detection of CYP2C9and VKORC1polymorphisms may have clinicalsignificance to guide the individualized warfarin dosage in lower extremity deep veinthrombosis patients. |
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