Genetic factors contribute to patient-specific warfarin dose for Han Chinese

Wang, Tingliang; Li, Honglei; Tjong, Wen-Ye; Chen, Qian-Su; Wu, Guan-Sheng; Zhu, Haitao; Hou, Zi-Shan; Xu, Shunqing; Ma, Shaolin; Wu, Madeline; Tai, Susan

doi:10.1016/j.cca.2008.07.005

Cited by 52 publications

(62 citation statements)

References 32 publications

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“…The allelic frequencies of CYP2C9*2 and CYP2C9*3 are considerably different in ethnic populations. 2,17 Our data was consistent with previous studies on Asia populations.…”

Section: Discussionsupporting

confidence: 93%

“…11 Recently, three independent white cohorts study demonstrated that a DNA variant in CYP4F2 was associated with warfarin dose and the difference of 1 mg per day in warfarin dose existed between CC and TT subjects. 2 We discovered that the daily warfarin doses of patients carrying TT genotype were significantly higher than those of patients carrying CC genotype. In whites and Asians, the minor allele frequency for rs2108622 is B30% compared with 7% in blacks.…”

Section: Discussionmentioning

confidence: 99%

“…1,20,21 In Asian patients, the multiple regression model based on the genetic polymorphisms and the nongenetic factors of age and body weight can explain 30-40% of the variance in warfarin dose. 2,4 Cho HJ et al suggested that it explained B32% of the overall variability in warfarin dose requirements given all of the variables studied in Koreans. 22 In Japanese patients, the model using the multiple regression analysis including age, sex, weight and three genetic polymorphisms accounted for 33.3% of total variations in warfarin dose.…”

Section: Discussionmentioning

confidence: 99%

“…1, 2 The effectiveness and safety of warfarin is dependent on maintaining the prothrombin time, expressed as the international normalized ratio (INR), within the therapeutic range. 1, 3 However, warfarin therapy is difficult due to a narrow therapeutic index and large inter-individual variability, which makes individual dosing necessary.…”

Section: Introductionmentioning

confidence: 99%

“…3,4 Moreover, recently it has been revealed that a genetic variation of cytochrome P450 4F2 (CYP4F2) is also associated with a clinically relevant effect of warfarin. 2,11 Common genetic variation in CYP4F2 (V433M) results in lower steady-state enzyme levels, possibly owing to enzyme instability leading to reduced capacity to metabolic vitamin K. 12 However, there are few reports describing the effects of these SNPs in Korean patients treated with warfarin up to the present.…”

Section: Introductionmentioning

confidence: 99%

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Proposal of pharmacogenetics-based warfarin dosing algorithm in Korean patients

et al. 2011

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Warfarin is a commonly prescribed anticoagulant drug for the prevention of thromboembolic disorders. We investigated the contribution of genetic variations of four genes and clinical factors to warfarin dose requirement and provided a warfarin-dosing algorithm based on genetic and clinical variables in Korean patients. We recruited 564 Korean patients on stable anticoagulation. Single nucleotide polymorphisms (SNPs) for the VKORC1, CYP2C9, CYP4F2 and GGCX were analyzed. Using multiple regression analysis, we developed a model to predict the warfarin requirement. The SNPs of VKORC1, CYP2C9, CYP4F2 and GGCX showed significant correlation with warfarin dose. Patients with the 3730AA genotype received significantly higher doses of warfarin than those with the 3730GG (P¼0.0001). For CYP2C9, the highest maintenance dose was observed in the patients with wild-type genotype compared with the variant allele carriers (Po0.0001). The multiple regression model including age, gender, body surface area (BSA), international normalized ratio (INR) and four genetic polymorphisms accounted for 35% of total variations in warfarin dose (R 2 ¼0.3499; Po0.0001). This study shows that age, gender, BSA, INR and VKORC1, CYP2C9 and CYP4F2 polymorphism affect warfarin dose requirements in Koreans. Translation of this knowledge into clinical guidelines for warfarin prescription may contribute to improve the efficacy and safety of warfarin treatment for Korean patients.

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“…The allelic frequencies of CYP2C9*2 and CYP2C9*3 are considerably different in ethnic populations. 2,17 Our data was consistent with previous studies on Asia populations.…”

Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Proposal of pharmacogenetics-based warfarin dosing algorithm in Korean patients

et al. 2011

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Pharmacogenomics Aspect of Warfarin Therapy

Krasowski

2012

Pharmacogenomics in Clinical Therapeutics

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VKORC1-1639G>A, CYP2C9, EPHX1691A>G genotype, body weight, and age are important predictors for warfarin maintenance doses in patients with mechanical heart valve prostheses in southwest China

Kong

Schneede

et al. 2010

Eur J Clin Pharmacol

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There were great interindividual differences in warfarin maintenance dosage (ranging from 0.6 to 8.4 mg/day) among the 127 patients with mechanical heart valve prostheses. VKORC1-1639G>A, CYP2C9, EPHX1691A>G polymorphism, body weight, and age were found to affect the dose demands. Multiple linear regression models incorporating genetic polymorphisms of VKORC1, CYP2C9, EPHX1691A>G, and the nongenetic factors of age and body weight were developed, and explained up to 76.8% of the total variation (adjusted R (2) of 0.743) in warfarin maintenance doses in southwest Chinese patients with mechanical heart valve prostheses.

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Genetic factors contribute to patient-specific warfarin dose for Han Chinese

Cited by 52 publications

References 32 publications

Proposal of pharmacogenetics-based warfarin dosing algorithm in Korean patients

Proposal of pharmacogenetics-based warfarin dosing algorithm in Korean patients

Pharmacogenomics Aspect of Warfarin Therapy

VKORC1-1639G>A, CYP2C9, EPHX1691A>G genotype, body weight, and age are important predictors for warfarin maintenance doses in patients with mechanical heart valve prostheses in southwest China

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