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Rapid Single-Nucleo...
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
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2009-04-01
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Oxford University Press (OUP),2009
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LIBRIS-ID:oai:DiVA.org:uu-98493
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-98493URI
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https://doi.org/10.1373/clinchem.2008.115295DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:118535177URI
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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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 and genre
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Yamamoto, Koujirou
(author)
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Oguchi-Katayama, Atsuko
(author)
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Kawai, Yuki
(author)
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Ishidao, Takefumi
(author)
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Mitani, Yasumasa
(author)
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Kogo, Yasushi
(author)
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Lezhava, Alexander
(author)
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Fujita, Yukiyoshi
(author)
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Obayashi, Kyoko
(author)
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Nakamura, Katsunori
(author)
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Kohnke, HugoUppsala universitet,Klinisk farmakologi(Swepub:uu)hukoh103
(author)
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Wadelius, MiaUppsala universitet,Klinisk farmakogenomik och osteoporos(Swepub:uu)miawadel
(author)
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Ekström, LenaKarolinska Institutet
(author)
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Skogastierna, CristineKarolinska Institutet
(author)
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Rane, AndersKarolinska Institutet
(author)
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Kurabayashi, Masahiko
(author)
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Murakami, Masami
(author)
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Cizdziel, Paul E.
(author)
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Hayashizaki, Yoshihide
(author)
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Horiuchi, Ryuya
(author)
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Uppsala universitetKlinisk farmakologi
(creator_code:org_t)
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In:Clinical Chemistry: Oxford University Press (OUP)55:4, s. 804-8120009-91471530-8561
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Aomori, Tohru
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Mitani, Yasumasa
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Kogo, Yasushi
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Kohnke, Hugo
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Wadelius, Mia
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Ekström, Lena
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Rane, Anders
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