| 18609070 |
Enstrom C, Osman A, Lindahl TL: A genotyping method for VKORC1 1173C> T by Pyrosequencing ((R)) technology. Drug Saf. 2009;32(3):203-18. doi: 10.2165/00002018-200932030-00003.
Vitamin K epoxide reductase complex subunit 1 (VKORC1) is the site of inhibition by warfarin and other anti-vitamin K drugs during oral anticoagulant therapy. The SNP rs9934438 in intron 1 of VKORC1 (c.173+1000C> T or 1173C> T) discriminating the VKORC1*2 haplotype is associated with low warfarin dose requirement and unstable prothrombin time - international normalized ratio. To genotype this SNP, we have developed a rapid method using Pyrosequencing ((R)) technology. The proposed method takes a post-PCR sample preparation of less than 1 h and a DNA sequencing time of less than 15 min to genotype 96 samples. The current method was compared with a dHPLC method that we reported previously. Genotype frequencies at VKORC1 1173C> T for our Swedish population were 38 % wild-type, 40 % heterozygote and 22 % homozygote. The frequency of the T-allele was 0.42, which exactly matches the frequency previously reported for Germans. The current method can be used to determine whether patients initiating warfarin therapy are carriers of SNP 1173 C> T that is strongly associated with low warfarin dose requirement. |
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