DNA sensors to assess the effect of VKORC1 and CYP2C9 gene polymorphisms on warfarin dose requirement in Chinese patients with atrial fibrillation.

摘要: The optimal dose of warfarin depends on polymorphisms in the VKORC1 (the vitamin K epoxide reductase complex subunit (1) and CYP2C9 (cytochrome P450 2C9) genes. To minimize risk adverse reactions, dosages should be adjusted according to results from rapid simple monitoring methods. However, there are few pharmacogenetic-guided dosing algorithms that based large cohorts Chinese population, especially patients with atrial fibrillation. This study aimed validate a algorithm new electrochemical detection method used multicenter study. Three SNPs (CYP2C9 *2, *3 c.-1639G > A) were genotyped by using sandwich-type format included 3' short thiol capture probe 5' ferrocene-labeled signal probe. A total 1285 samples four clinical hospitals evaluated. Concordance rates between DNA biosensor sequencing test 99.8%. for gene distribution showed most had higher susceptibility because mutant-type heterozygotes present majority subjects (99.4%) at locus c.-1639G > A. When International Warfarin Pharmacogenetics Consortium was estimate therapeutic 362 AF values compared their actual dosages, revealed 56.9% similar (within 20% range). novel *3and c.-1639G > A alleles data gathered patient cohort can facilitate reasonable effective use AF.