The Correlational Research Between VKORC1-1639G/A Gene Polymorphism And Warfarin Dose Of Han Population In Henan Province

Objective:The study was to explore the relationship between VKORC1-1639 G/A gene phenotype and warfarin maintain dose in Han population of Henan Province. Probe the distributions of VKORC1-1639 G/A gene phenotype and alleles in Han population of Henan Province, and compare them with Chinese Han population in other areas and other ethnic groups. Probe the relationship between warfarin maintain dose and VKORC1-1639 G/A gene polymorphism, gender, age, body mass index (MBI), international normalized ratio (INR), and establish the multiple regression equation, guide individual therapy of warfarin.Method:Screened patients used warfarin as, collected general informations:ethnic group, gender, age, height, weight, disease, duration of oral anticoagulation and maintain warfarin dose. Selected 112 patients used warfarin (2.5mg/piece) produced by the Shanghai Xin Yi Pharmaceutical Company. The research subjects were using maintain dose warfarin and the INR was between 1.8 and 3.0.2ml peripheral venous bloods were taken from each patient for DNA extracted. Detected the VKORC1-1639G/A genotypes. Calculated the distribution and frequencies of gene phenotypes and allele frequencies used statistical study. The result of VKORC1-1639 G/A polymorphism of this study was compared with other ethnic groups. The warfarin maintain dose was compared between different VKORC1-1639G/A gene phenotypes. Calculated the body mass index (BMI) based on the objects' heights and weights. Analyzed the affections for warfarin maintain dose by the VKORC1-1639 G /A gene polymorphism, sex, age, international normalized ratio and BMI, established multiple linear regression equation.Result:VKORC1-1639 G/A gene polymorphism distribution of the 112 cases:93 cases for AA genotype (83.00%),18 cases for GA genotype (16.10%) and 1 case for GG genotypes (0.90%). A allele frequency 204(91.07%), G allele frequency 20(8.93%).Compared distributions of VKORC1-1639 G/A gene phenotypes and alleles of this study with other Han Chinese populations, the differences was not statistically significant, but compared the distributions with other ethnic groups, the differences were statistical(p<0.01). Different maintain dose warfarin was used in different gene phenotypes, (2.44±0.45)mg/d for AA genotype and (4.67±0.89)mg/d for AG and GG genotypes. The difference between them was statistically significant (p<0.01).Established multiple linear regression equation based on VKORC1-1639 G/ A gene polymorphism, sex, age, international normalized ratio and BMI: y=-0.719+2.127(VKORC1-1639 G/A gene polymorphism)+0.632 (INR)-0.11(gender)-0.256(age, year)+0.29 (BMI,Kg/m2) (r=0.909, r2=0.826, p<0.01)Conclusion:1. VKORC1-1639 G/A gene polymorphism are obvious in Han population in Henan Province, the most was AA genotype, GG genotype was extremely rare.2. Compared distributions of VKORC1-1639 G/A gene phenotypes and alleles of Han Chinese people in Henan province with other Han Chinese populations, the differences was not statistically significant, but compared distributions with other ethnic groups, the differences were statistical. The result further confirmed that VKORC1-1639G/A polymorphism were related with warfarin diversity inter-ethnic.