Associaton Between VKORC1Genetic Polymorphism And Other Factors And Aged People Warfarin Dose Requirement

Objective To assess the contribution of VKORC11639G>A VKORC11173C>T VKORC13730A>G genetic polymorphism and aged people Warfarin dose requirement. A multivariable regression equation is established including sex, age, height, weight, BSA, VKORCI to predict stable warfarin dose requirement in aged people,to safely and efficiently prescribe warfarin for different aged patients.Methods A case-control study was performed on170aged subjects,88patie-nts with stable wafarin dose requirement were enrolled as experimental group,the average age of this group was71.17±5.12years old,82normal indivaduals for annumal health examination were erolled as control group, the average age was70.50±3.27yeares old. All these cases were from The First Hospital of Kunming Medical University.Blood samples were taken for VKORCI genotyping from these170subjects,DNAs were extracted from these samples, and amplified via PCR, then the PCR products were identified by gel electrophoresis and detected to the mutation with ABI-PRISM3730, in order that we obtained the distribution frequency of VKORCI polymorphism of these three sets, H-W test and linkage disequilibrium test were made for all these three genetic locus. Further more, analysed the relationship between VKORCI poly-morphism and wafarin dose requirement, and anassessed the effect of clinical factors and genetics on the stable wafarin dose requirement.Results Patients with VKORCI1639AA genotype required a significantly lower warfarin dose than those with GA genotype[(2.59±0.69mg/d) vs (4.26±0.56mg/d)]. There was no significantly difference between the experimental group and the control group in the VKORC11639genetic frequencies. The frequencies results showed that the frequencies of homozygous(AA), heterozygous(GA) and wide-type homozygous(GG) of VKORC11639G>A in the experimental group were81.8%, 18.2%,0.0%respectively. The frequencies AA, GA and GG of VKORCl1639G>A in the control group were82.9%,17.1%,0.0%, respectively.And patients with VKORC11173TT genotype still required a significantly lower warfarin dose than those with CT genotype [(2.62±0.73mg/d) vs (4.21±0.55mg/d)]. The frequencies of homozygous (TT), heterozygous(CT) and wide-type homozygous(CC) of VKORC11173C>T in the experimental group were83.0%,17.0%,0.0%respectively. The frequencies TT, CT and CC of VKORC11173CT in the control group were82.9%,17.1%,0.0%respectively. the two groups compared with each other, there was no significantly difference in the VKORC11173genetic frequencies. Patients with VKORC13730GG genotype required a significantly lower warfarin dose than those with GA genotype [(2.61±0.69mg/d) vs (4.14±0.81mg/d)]. It's also no significantly difference between the experimental group and the control group in the VKORC13730genetic frequencies, the frequencies of homozygous(GG), heterozygous(GA) and wide-type homozygous(AA) of VKORC13730A>G in the experimental group were81.8%,18.2%,0.0%respectively,and the frequencies GG, GA and AA of VKORC13730A>G in the control group were82.9%,17.1%,0.0%respectively. The multiple linear regression equation for wafarin dose indicate weight and VKORC11639genotype is IN(D)=-0.294+0.01×weight(kg)+0.521X VKORC11639genotype(VKORC11639AA=1, VKORC11639GA=2), R2=0.472, Adjusted R2=0.459(P=0.000)Conclusion In our study, heterozygoumutation need a lower warfarin dosage than homozygous. The data showes that weight and VKORC1polymorphism have a significant influence on wafarin dose requirement.The multiple linear regression equation for wafarin dose indicate weight and VKORC11639genotype could explain the inter-individual variation in dose requirement of47.2%. VKORC11639G>A VKORC11173C>T and VKORC13730A>G polymorphism have sronger linkage disequilibrium between each other. There are statistically differentce in the distri-bution of VKORC1genetic frequencies between our subjects and othere population.