TY - JOUR
T1 - 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
AU - Aomori, Tohru
AU - Yamamoto, Koujirou
AU - Oguchi-Katayama, Atsuko
AU - Kawai, Yuki
AU - Ishidao, Takefumi
AU - Mitani, Yasumasa
AU - Kogo, Yasushi
AU - Lezhava, Alexander
AU - Fujita, Yukiyoshi
AU - Obayashi, Kyoko
AU - Nakamura, Katsunori
AU - Kohnke, Hugo
AU - Wadelius, Mia
AU - Ekströ, Lena
AU - Skogastierna, Cristine
AU - Rane, Anders
AU - Kurabayashi, Masahiko
AU - Murakami, Masami
AU - Cizdziel, Paul E.
AU - Hayashizaki, Yoshihide
AU - Horiuchi, Ryuya
PY - 2009/4/1
Y1 - 2009/4/1
N2 - Background: Polymorphisms of the CYP2C9 (cytochrome P450, family 2, subfamily C, polypeptide 9) gene (CYP2C92, CYP2C93) 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 CYP2C92, CYP2C93, 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 after 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.
AB - Background: Polymorphisms of the CYP2C9 (cytochrome P450, family 2, subfamily C, polypeptide 9) gene (CYP2C92, CYP2C93) 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 CYP2C92, CYP2C93, 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 after 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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U2 - 10.1373/clinchem.2008.115295
DO - 10.1373/clinchem.2008.115295
M3 - Article
C2 - 19181737
AN - SCOPUS:64149111606
SN - 0009-9147
VL - 55
SP - 804
EP - 812
JO - Clinical Chemistry
JF - Clinical Chemistry
IS - 4
ER -