uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
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
Show others and affiliations
2009 (English)In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 55, no 4, 804-812 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2009. Vol. 55, no 4, 804-812 p.
National Category
Medical and Health Sciences Pharmacology and Toxicology
URN: urn:nbn:se:uu:diva-98493DOI: 10.1373/clinchem.2008.115295ISI: 000264774200026PubMedID: 19181737OAI: oai:DiVA.org:uu-98493DiVA: diva2:174701
Available from: 2009-02-24 Created: 2009-02-24 Last updated: 2016-02-19

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Wadelius, Mia
By organisation
Clinical PharmacologyClinical pharmacogenomics and osteoporosis
In the same journal
Clinical Chemistry
Medical and Health SciencesPharmacology and Toxicology

Search outside of DiVA

GoogleGoogle Scholar

Altmetric score

Total: 200 hits
ReferencesLink to record
Permanent link

Direct link