Novel genetic variants in Asian subjects and their influence on maintenance warfarin dose

• DOI: 10.1016/j.clpt.2004.05.005
• Publication Date: 2004-09-16T14:10:39Z
• Authors: F ZHAO; C LOKE; S RANKIN; J GUO; H LEE; T WU; T TAN; T LIU; W LU; Y LIM
• Keywords: Malay; VKORC1; Maintenance dose; Nonsynonymous substitution

Background Commonly occurring genetic variants in CYP2C9 are known to reduce catalytic activity and associated with enhanced patient sensitivity warfarin. Interethnic differences warfarin dose requirement have been described the Asian population, we postulate that this could be related of unique ethnic groups. Methods We prospectively genotyped 125 patients who were receiving a stable daily maintain international normalized ratio values between 2 3 through comprehensive sequencing promoter coding regions gene. Results The mean weight-adjusted maintenance was significantly lower for Malay Chinese subjects than Indian (P < .001 .014, respectively). Warfarin negatively correlated age (r = −0.4, P .001) but not sex. Multiple detected promoter, exonic, intronic, 3′-untranslated CYP2C9, which 16 novel, including 7 nonsynonymous exonic (208G>C, 374G>A, 485C>A, 895A>G, 1144C>T, 1190A>C, 1362G>C). CYP2C9*3, CYP2C9*2, found patients, carriers CYP2C9*3 variant .01) .77), required less influence novel on unclear, because they rare, existed despite omission individuals any region from analysis. Conclusions dosing may result other genetic, dietary, or environmental influences; however, these gene warrant further characterization functional studies. Clinical Pharmacology & Therapeutics (2004) 76, 210–219; doi: 10.1016/j.clpt.2004.05.005