Genetic polymorphism in exon 4 of cytochrome P450 CYP2C9 may be associated with warfarin sensitivity in Chinese patients

Pharmacogenetics of CYP2C9 and interindividual variability in anticoagulant response to warfarin

“…Recently, different groups of investigators have reported the relation between CYP2C9 polymorphisms (ie, CYP2C9*2 and CYP2C9*3) and the daily dose requirement of warfarin and risks of bleeding complications during anticoagulation therapy. [22][23][24][25][26][27][28][29][30][31][32] These studies support an idea that the genetic polymorphisms of CYP2C9 would contribute to the interindividual variability of the anticoagulation responses to warfarin along with the previously known clinical and environmental variables (eg, age, concomitantly administered drugs, foods and clinical indications). 33,34 Our knowledge about pharmacodynamic factors associated with the variability in the anticoagulation of warfarin is relatively limited.…”

“…We critically reappraised their findings using their primers originally reported by Stubbins et al 43 and the other primers by Sullivan-Klose et al 44 that were validated by us and others. [12][13][14]16 We found that the nucleotide sequences of the PCR products amplified by the primers of Leung et al 32 and Stubbins et al 43 differed from those amplified by the latter primers 44 and the authentic DNA sequence of CYP2C9 exon 4. Using the latter PCR primers we found no SNPs in exon 4 of CYP2C9 in Japanese patients (unpublished data).…”

“…The Caucasian patients with the CYP2C9*1/*3 and CYP2C9*3/*3 genotypes have 20-45% and 75% lower warfarin doses than those with homozygous wild-type CYP2C9 genotype, respectively. 15,[24][25][26][27][28][29][30][31] Anecdotal observations indicated that the maintenance doses of warfarin obtained from Asians (ie, 3.4 and 3.3 mg/day for Japanese [12][13][14] and Chinese, 32 respectively) are 20-50% lower than those obtained from Caucasian (ie, 4.1-6.7 mg/day). 10,11,[22][23][24][25][26][27][28][29][30][31] We will discuss whether or not the assumed population difference in the maintenance dose of warfarin between Caucasians and Asians can be explained by the population difference in the polymorphisms of CYP2C9 in the separate chapter.…”

Accuracy assessment of pharmacogenetic algorithms for warfarin dose prediction in Chinese patients

“…Recent pharmacogenetic studies showed that variations in genes, especially vitamin-K epoxide reductase complex subunit 1 (VKORC1) and cytochrome P450 family 2 subfamily C polypeptide 9 (CYP2C9), contributed significantly to differences in warfarin dose requirements among patients, along with clinical and demographic factors [2][3][4][5]. Subsequent to these investigations, in 2007 the US Food and Drug Administration added pharmacogenetic information to the warfarin product label, highlighting the benefits of genotyping individual patients to improve the initial estimate of a reasonable warfarin dose [6].…”

“…IkeOluwa Lagunju, 1,2 * Olugbemiro Sodeinde, 1,2 and Paul Telfer 3,4 Transcranial Doppler (TCD) ultrasonography helps to identify children with sickle cell disease (SCD) who are at an increased risk of stroke, making primary stroke prevention a reality. A cross-sectional study of 145 Nigerian children aged 3 years with SCD was carried out to describe the pattern of cerebral blood flow (CBF) abnormalities.…”