Ethnic differences in CYP2C9*2 (Arg144Cys) and CYP2C9*3 (Ile359Leu) genotypes in Japanese and Israeli populations

Nakai, Kenta; Habano, Wataru; Nakai, Keiko; Fukushima, Noriko; Suwabe, Akira; Moriya, Shogo; Osano, Kaoru; Genevieve, David

doi:10.1016/j.lfs.2005.04.049

Cited by 37 publications

(21 citation statements)

References 18 publications

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“…This observation has been confirmed by some multiethnic studies conducted in Asia including patients belonging to different Asian countries. 38,53,54 So each region should be treated as an individual entity. A small part of human genome is playing its part in this genetic diversity, as the major part has been found to be similar among humans.…”

Section: Discussionmentioning

confidence: 99%

Frequency of Common CYP2C9 Polymorphisms and Their Impact on Warfarin Dose Requirement in Pakistani Population

Qayyum

Najmi

Mansoor

et al. 2016

Clin Appl Thromb Hemost

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Polymorphisms in cytochrome P450 (CYP) 2C9 (CYP2C9) gene result in interindividual variability in warfarin dose requirement. There is a need for characterization of genotype frequency distribution in different populations for construction of customized dosing algorithms to enhance the efficacy and reduce the toxicity of warfarin therapy. This study was carried out in Pakistani population to evaluate the contribution of common CYP2C9 polymorphisms to warfarin therapy. A total of 550 stable patients taking warfarin were enrolled after medical history, physical examination, and laboratory investigations. Single blood sample was collected after informed consent. Genomic DNA was extracted, and genotype analysis for CYP2C9*2 and CYP2C9*3 polymorphisms was done by polymerase chain reaction-restriction fragment length polymorphism assay. A number of samples were also analyzed by direct DNA sequencing for validation of the results. Data were analyzed using SPSS version 20. Genotype frequency distribution of CYP2C9*2 and CYP2C9*3 was found to be different from other populations. Of these 2 polymorphisms, CYP2C9*2 did not demonstrate significant effect on warfarin dose requirement, whereas CYP2C9*3 did show significant effect ( P value = .012). It is concluded that there is a need to study genotype frequency distribution and their effect on warfarin dose variability among different populations due to diversity in outcome.

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Section: Discussionmentioning

confidence: 99%

Frequency of Common CYP2C9 Polymorphisms and Their Impact on Warfarin Dose Requirement in Pakistani Population

Qayyum

Najmi

Mansoor

et al. 2016

Clin Appl Thromb Hemost

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“…[6][7][8][9][10][11][12] In recent years, Mushiroda, et al reported that the CYP2C9 and VKORC1 haplotype may affect the warfarin maintenance dose. 13) Our group has also shown that there are ethnic differences in terms of the genetic polymorphism of CYP2C9 and VKORC1, 14,15) which suggests that the optimal warfarin dose could vary between ethnicities.…”

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confidence: 93%

Clinical Significance of Combined CYP2C9 and VKORC1 Genotypes in Japanese Patients Requiring Warfarin

2011

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SummaryThe individual management of anticoagulation therapy is important for safe medical outcomes, including those of oral surgery. Here, Japanese patients who received warfarin (n = 35) and normal controls (n = 125) were analyzed by real-time PCR to determine the frequencies of single nucleotide polymorphisms in VKORC1 (vitamin K epoxide reductase complex, subunit 1) and CYP2C9 and how these frequencies related to warfarin dose and PT-INR. The genetic polymorphisms CYP2C9 *2 (416 C > T), CYP2C9 *3 (1061 A > C), and intron 1-136 C > T in VKORC1 (1173 C > T) were measured. All patients had the wild-type CYP2C9 gene (*1/*1). All 160 cases had the wild-type (CC) type CYP2C9 *2 , 93.8% had AA type CYP2C9 *3 , 6.2% had AC type CYP2C9 *3 , 1.2% had CC type VKORC1, 13.8% had CT type VKO-RC1, and 85% had TT type VKORC1. The CC type VKORC1 genetic polymorphism was associated with a significantly higher mean warfarin maintenance dose (4.5 ± 0.5 mg) than other VKORC1 genotypes (TT type 2.9 ± 0.1 mg: CT type 3.4 ± 0.3 mg). Categorization of the patients in terms of the combined CYP2C9 and VKORC1 haplotype (the warfarinresponsive index; WRI) revealed the mean daily warfarin maintenance dose was 3.0 ± 0.1 mg for WRI 1 and 3.7 ± 0.3 mg for WRI 2 (P < 0.012). The event survey revealed 2 patients with nonfatal cerebral hemorrhage had a WRI score of 2 (VKORC1 C/T heterozygosity genotype). Thus, CYP2C9 and VKORC1 haplotype analysis allows prediction of warfarin maintenance dosage. The findings may provide a personalized use of warfarin in the field of oral surgery. (Int Heart J 2011; 52: 44-49)

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“…Ethnic differences in the distribution of these pharmacogenetically relevant gene polymorphisms in CYP2C9 and VKORC1 have been reported in a variety of populations [12][13][14][15], demonstrating that the relative contribution of these polymorphisms to warfarin dosing is population dependent, with obvious implications for pharmacogenetic clinical testing. Thus, for instance, though the VKORC1 genotype is of limited predictive value in AfroAmericans [16,17] it is of utmost value in individuals of Asian descent [18].…”

Section: Introductionmentioning

confidence: 99%

“…Despite the wealth of data regarding the distribution of CYP2C9 and VKORC1 polymorphisms across a variety of populations worldwide, including Ashkenazi and Sephardi Jews [12][13][14][15], little is currently known about the distribution of these variants in the highly heterogeneous Israeli population, comprised of distinct ethnic/religious subpopulations with negligible rates of inter marriage.…”

Section: Introductionmentioning

confidence: 99%

Distribution of CYP2C9 and VKORC1 Risk Alleles for Warfarin Sensitivity and Resistance in the Israeli Population

Efrati

Elkin²,

Sprecher³

et al. 2010

CDS

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Ethnic differences in CYP2C92 (Arg144Cys) and CYP2C93 (Ile359Leu) genotypes in Japanese and Israeli populations

Cited by 37 publications

References 18 publications

Frequency of Common CYP2C9 Polymorphisms and Their Impact on Warfarin Dose Requirement in Pakistani Population

Frequency of Common CYP2C9 Polymorphisms and Their Impact on Warfarin Dose Requirement in Pakistani Population

Clinical Significance of Combined CYP2C9 and VKORC1 Genotypes in Japanese Patients Requiring Warfarin

Distribution of CYP2C9 and VKORC1 Risk Alleles for Warfarin Sensitivity and Resistance in the Israeli Population

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