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  • Aomori, Tohru (author)

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

  • Article/chapterEnglish2009

Publisher, publication year, extent ...

  • 2009-04-01
  • Oxford University Press (OUP),2009
  • printrdacarrier

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  • LIBRIS-ID:oai:DiVA.org:uu-98493
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-98493URI
  • https://doi.org/10.1373/clinchem.2008.115295DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:118535177URI

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  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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.

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  • Yamamoto, Koujirou (author)
  • Oguchi-Katayama, Atsuko (author)
  • 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, HugoUppsala universitet,Klinisk farmakologi(Swepub:uu)hukoh103 (author)
  • Wadelius, MiaUppsala universitet,Klinisk farmakogenomik och osteoporos(Swepub:uu)miawadel (author)
  • Ekström, LenaKarolinska Institutet (author)
  • Skogastierna, CristineKarolinska Institutet (author)
  • Rane, AndersKarolinska Institutet (author)
  • Kurabayashi, Masahiko (author)
  • Murakami, Masami (author)
  • Cizdziel, Paul E. (author)
  • Hayashizaki, Yoshihide (author)
  • Horiuchi, Ryuya (author)
  • Uppsala universitetKlinisk farmakologi (creator_code:org_t)

Related titles

  • In:Clinical Chemistry: Oxford University Press (OUP)55:4, s. 804-8120009-91471530-8561

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