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Rapid Single-Nucleotide Polymorphism Detection of Cytochrome P450 (CYP2C9) and Vitamin K Epoxide Reductase (VKORC1) Genes for the Warfarin Dose Adjustment by the SMart-Amplification Process Version 2

Aomori, Tohru (author)
Yamamoto, Koujirou (author)
Oguchi-Katayama, Atsuko (author)
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Kawai, Yuki (author)
Ishidao, Takefumi (author)
Mitani, Yasumasa (author)
Kogo, Yasushi (author)
Lezhava, Alexander (author)
Fujita, Yukiyoshi (author)
Obayashi, Kyoko (author)
Nakamura, Katsunori (author)
Kohnke, Hugo (author)
Uppsala universitet,Klinisk farmakologi
Wadelius, Mia (author)
Uppsala universitet,Klinisk farmakogenomik och osteoporos
Ekström, Lena (author)
Karolinska Institutet
Skogastierna, Cristine (author)
Karolinska Institutet
Rane, Anders (author)
Karolinska Institutet
Kurabayashi, Masahiko (author)
Murakami, Masami (author)
Cizdziel, Paul E. (author)
Hayashizaki, Yoshihide (author)
Horiuchi, Ryuya (author)
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 (creator_code:org_t)
2009-04-01
2009
English.
In: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 55:4, s. 804-812
Related links:
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https://doi.org/10.1...
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • BACKGROUND: Polymorphisms of the CYP2C9 (cytochrome P450, family 2, subfamily C, polypeptide 9) gene (CYP2C9*2, CYP2C9*3) and the VKORC1 (vitamin K epoxide reductase complex, subunit 1) gene (-1639G>A) greatly impact the maintenance dose for the drug warfarin. Prescreening patients for their genotypes before prescribing the drug facilitates a faster individualized determination of the proper maintenance dose, minimizing the risk for adverse reaction and reoccurrence of thromboembolic episodes. With current methodologies, therapy can be delayed by several hours to 1 day if genotyping is to determine the loading dose. A simpler and more rapid genotyping method is required. METHODS: We developed a single-nucleotide polymorphism (SNP)-detection assay based on the SMart Amplification Process version 2 (SMAP 2) to analyze CYP2C9*2, CYP2C9*3, and VKORC1 -1639G>A polymorphisms. Blood from consenting participants was used directly in a closed-tube real-time assay without DNA purification to obtain results within 1 h of blood collection. RESULTS: We analyzed 125 blood samples by both SMAP 2 and PCR-RFLP methods. The results showed perfect concordance. CONCLUSIONS: The results validate the accuracy of the SMAP 2 for determination of SNPs critical to personalized warfarin therapy. SMAP 2 offers speed, simplicity of sample preparation, the convenience of isothermal amplification, and assay-design flexibility, which are significant advantages over conventional genotyping technologies. In this example and other clinical scenarios in which genetic testing is required for immediate and better-informed therapeutic decisions, SMAP 2-based diagnostics have key advantages.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)

Keyword

MEDICINE
MEDICIN
Clinical pharmacology
Klinisk farmakologi

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