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Method for auxiliarily determining warfarin dosage for Chinese Han patients by utilizing single nucleotide polymorphism analysis and biological chip

A single nucleotide polymorphism and biochip technology, which is applied in the field of auxiliary determination of the dosage of warfarin in Chinese Han patients, can solve the problems of limited Caucasians

Inactive Publication Date: 2009-09-30
李文正纳米研究院
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] Some latest studies have shown that single nucleotide polymorphisms (Single nucleotide polymorphisms, SNPs) at multiple sites on the above three genes have a significant impact on the safe dosage of the drug warfarin, but most of these current studies are limited to whites. within the range of human species (see Wadelius M, Chen LY, Eriksson N, Bumpstead S, Ghori J, Wadelius C, Bentley D, McGinnis R, Deloukas P (2007) Association of warfarin dose with genes involved in its action and metabolism. Hum Genet 121:23-34.)
At present, there is no comprehensive report in the field on the correlation between the single nucleotide polymorphism sites on these genes and the dosage of the drug warfarin in the Chinese Han race

Method used

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  • Method for auxiliarily determining warfarin dosage for Chinese Han patients by utilizing single nucleotide polymorphism analysis and biological chip
  • Method for auxiliarily determining warfarin dosage for Chinese Han patients by utilizing single nucleotide polymorphism analysis and biological chip
  • Method for auxiliarily determining warfarin dosage for Chinese Han patients by utilizing single nucleotide polymorphism analysis and biological chip

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0088] This model is the most simple model. In addition to relevant environmental factors, it calculates the safe dosage of warfarin for Chinese Han patients based on the data of only two parameters, body weight and age. The regression equation is: D=(2.375±0.753)+(0.024±0.010)×BW−(0.018±0.008)×Age (p<0.001).

Embodiment 2

[0089] In addition to relevant environmental factors, body weight and age, the model added the genotype detection data of the rs9934438 site of the VKORC1 gene to calculate the safe dosage of warfarin for Chinese Han patients. The regression equation is: D=(2.187±0.635)+(0.026±0.009)×BW-(0.022±0.006)×Age+(2.010±0.228)×(VKORC1_rs9934438: TT=0; TC=1; CC=2)( p<0.001).

Embodiment 3

[0090] In addition to the relevant environmental factors, body weight and age, the model added the genotype detection data of the rs1057910 and rs9332127 sites of the CYP2C9 gene to calculate the safe dosage of warfarin for Chinese Han patients. The regression equation is: D=(2.250±0.735)+(0.025±0.010)×BW-(0.013±0.007)×Age-(0.930±0.341)×(CYP2C9_rs1057910: AA=0; AC=1; CC=2) -(0.765±0.376)×(CYP2C9_rs9332127: GG=0; GC=1; CC=2) (p<0.001).

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Abstract

The invention relates to a method for auxiliarily determining warfarin dosage for Chinese Han patients by utilizing single nucleotide polymorphism analysis and a biological chip. In particular, the invention provides a method for acquiring grades useful in determining the warfarin dosage for the Chinese Han patients, which comprises the following steps: (1) acquiring a nucleic acid sample from a patient; (2) detecting the nucleic acid sample aiming at one or more single nucleotide polymorphism sites selected from the following groups: rs9934438 site of VKORC1 gene, rs1057910 site and rs9332127 site of CYP2C9 gene, and rs4653436 site of EPHX1 gene; (3) determining genotypes of the single nucleotide polymorphism sites; and (4) grading the genotypes of the single nucleotide polymorphism sites, wherein the grades obtained in step (4) are helpful in determining the warfarin dosage for the patient. The invention also provides the biological chip used for the method.

Description

technical field [0001] The invention relates to an auxiliary method for determining the dose of warfarin used by Chinese Han patients. More specifically, the present invention relates to 4 single nucleotide polymorphism sites on 3 genes (VKORC1, CYP2C9 and EPHX1) related to warfarin metabolic kinetics and pharmacodynamics, and these single nucleotide polymorphisms The application of acid polymorphism loci in predicting the safe dosage of drug warfarin in different individuals of Chinese Han race. Background technique [0002] Warfarin (Warfarin, also known as "warfarin") is the most commonly used coumarin-type oral strong anticoagulant drug in clinical practice, and is widely used in heart valve replacement, atrial fibrillation, pulmonary embolism, and recurrent stroke (stroke) Prevention and treatment of deep arteriovenous thrombotic diseases. The chemical structure of the drug is 3-(a-phenylacetone)-4-hydroxycoumarin, which is a racemic mixture of two optical isomers R-t...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/68
Inventor 王廷亮李红蕾吴汪黔生戴书文
Owner 李文正纳米研究院
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