Yunnan Han Population CYP2C9 Gene Polymorphism And Warfarin Dose Treatment Of Correlation Study

Objective:As a derivant of bishydroxyeoumarin, warfarin is the most commomly Preseribed oral antieogulant when it was invented. For the narrow therapeutic index, it is easy to lead to adverse effects, such as thrombogenesis or bleeding. Another characteristic of warfarin therapy is the large different stable dose between different races as well as inter-individuals, with more than20-fold of the stable dose range. As such, it is difficult for clinicians to safely and efficiently prescribe warfarin for diffenent patients. Multiple factors affect the inter individual variation of warfarin dose, inclued gender, body surface area, drug interactions dietary and morbid state.However, the effect of genetic factors on the variation of warfarin dose is more important. At present, there are more than 30 genes related to the Pharmacodynamics and pharmacokinetics of warfarin, and Cytochrome P450 2C9 (CYP2C9) and VitaminK epoxide reduetase eomplex subunit 1 gene (VKORC1) are the two most important genetic factors. In the present study, we invest the association of CYP2C9 (CYP2C9*2,CYP2C9*3,CYP2C9*c₆5) three gene polymorphism with warfarin in Yunnan Han population, and may give the new evidence for molecular heredity and the dependent factors inter-subject of warfarin dose. To invest the relevance of warfarin dose and CYP2C9, and may give the new evidence for mechanism and gene diagnosis for inter-individuals warfarin treatment. blood from coagulating, DNA was extracted, Genotype and allele frequencies of polymorphism in three genes were examined by polymerase chain reaction and restriction fragement length polymorphism (PCR-RFLP) technique in 300 warfarin using patients. All statistics were performed on SPSS 15.0 and Arlequin.Results:There is only C allele found of CYP2C9*2 in warfarin using patients,There was no found gene mutation at gene locus CYP2C9*2,and there was no correlation between warfarin dose and polymorphism for CYP2C9*2.There are two alleles(C,A) and three genotypes (A/A,A/C,C/C) at gene locus CYP2C9*3. Genotype A/A were found in 276 cases (92%), The warfarin dose is 3.34±1.17mg; genotypes A/C were foud in 22 cases (7.3%), The warfarin dose is 2.71±1.03mg; genotypes C/C were foud in 2 cases (0.7%), The warfarin dose is 0.81±0.26mg. The frequency of A allele is 95.7%, the frequency of C allele is 4.3%. The genotype and allele frequencies of CYP2C9*3 polymorphism siffered significantly, P=0.0003 (p<0.05),there was significant correlation between warfarin dose and polymorphism for CYP2C9*3, The frequency of genotype C/C in Yunnan group need lower warfarin dose.There are two alleles,C) and two genotypes (G/G,G/C) at gene locus CYP2C9*c₆5. Genotype G/G were found in 281 cases (93.7%), genotypes G/C were foud in 19 cases (6.3%), The frequency of G allele is 96.9%, the frequency of C allele is 3.2%. Genotype and allele frequency of CYP2C9*c₆5 was not statistically significant, P= 0.627 (P>0.05), there was no significant correlation between warfarin dose and polymorphism for CYP2C9*c₆5.There is no significant association of gene loci between CYP2C9*3 CYP2C9*c₆5 polymorphism and gender differences in Yunnan group.Lingkage disequilibrium analysis shows that there is a strong linkage between CYP2C9*3 and CYP2C9*c₆5 in Han majority of Yunnan province (D'=0.72). Conclusion:There is no significant association of gene loci between CYP2C9*2 CYP2C9*c₆5 polymorphism and warfarin dose in Yunnan group. CYP2C9*3 gene polymorphism is related to warfarin dose,The frequency of three genotypes at this gene locus has statistical significant difference, The genotype C/C in Yunnan Han population need lower warfarin dose.