Allele and genotype frequencies of <i>CYP2C9</i> in a Korean population

Bae, Jung‐Woo; Kim, Hyun-Kyung; Kim, Ji Eun; Yang, Sang-In; Kim, Mi-Jeong; Jang, Choon‐Gon; Lee, Seok‐Yong

doi:10.1111/j.1365-2125.2005.02448.x

Cited by 82 publications

(88 citation statements)

References 21 publications

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“…Thereafter, this allele was also found in Koreans (allele frequency ϭ 0.006) (Bae et al, 2005) and Japanese (allele frequency ϭ 0.0014 -0.002) (Maekawa et al, 2006, Yin et al, 2008, indicating that it is a relatively common allele among East Asians. In our baculovirus-insect cell system, total (apo and holo forms) CYP2C9 expression levels determined by Western blotting were not significantly different between CYP2C9.1 and CYP2C9.13 (Fig.…”

Section: Discussionmentioning

confidence: 97%

“…More recently, a series of novel nonsynonymous variations were identified in several Asian populations (Si et al, 2004;Zhao et al, 2004;Maekawa et al, 2006;Yin et al, 2008). *13 (L90P), an allele originally identified in a Chinese poor metabolizer toward lornoxicam, has been found in Chinese, Korean, and Japanese individuals at allele frequencies of 0.002 to 0.01 (Si et al, 2004;Bae et al, 2005;Maekawa et al, 2006;Yin et al, 2008). CYP2C9.13 was reported to show decreased enzymatic activity toward lornoxicam, tolbutamide, and diclofenac in vivo and/or in vitro (Guo et al, 2005a,b).…”

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confidence: 99%

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Substrate-Dependent Functional Alterations of Seven CYP2C9 Variants Found in Japanese Subjects

Maekawa

Harakawa²,

Sugiyama³

et al. 2009

Drug Metab Dispos

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ABSTRACT:CYP2C9 is a polymorphic enzyme that metabolizes a number of clinically important drugs. In this study, catalytic activities of seven alleles found in Japanese individuals, CYP2C9*3 (I359L), *13 (L90P), *26 (T130R), *28 (Q214L), *30 (A477T), *33 (R132Q), and *34 (R335Q), were assessed using three substrates (diclofenac, losartan, and glimepiride). When expressed in a baculovirus-insect cell system, the holo and total (apo and holo) CYP2C9 protein expression levels were similar among the wild type (CYP2C9.1) and six variants except for CYP2C9. CYP2C9 is a polymorphic enzyme responsible for the oxidative metabolism of up to 15% of the drugs that undergo phase I metabolism (Miners and Birkett, 1998). This enzyme hydroxylates weakly acidic or neutral drugs of diverse therapeutic categories, including the hypoglycemic agents tolbutamide and glimepiride, the nonsteroidal anti-inflammatory drugs flurbiprofen and diclofenac, the antihypertensive losartan, the diuretic torsemide, the anticonvulsant phenytoin, and the anticoagulant warfarin (Rettie and Jones, 2005). To date, 34 CYP2C9 alleles located in the coding region have been reported

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Section: Discussionmentioning

confidence: 97%

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confidence: 99%

Substrate-Dependent Functional Alterations of Seven CYP2C9 Variants Found in Japanese Subjects

Maekawa

Harakawa²,

Sugiyama³

et al. 2009

Drug Metab Dispos

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“…The CYP2C9*3 allele is less common (0.033−0.162) [3] . In contrast, the CYP2C9*2 allele is rare among East Asians [3,4] , and CYP2C9*3 is more common than that in Europeans (0.007 to 0.060) [5] . In addition, CYP2C9*3 homozygotes are seldom detected in East Asian populations [5] .…”

Section: Introductionmentioning

confidence: 92%

“…In contrast, the CYP2C9*2 allele is rare among East Asians [3,4] , and CYP2C9*3 is more common than that in Europeans (0.007 to 0.060) [5] . In addition, CYP2C9*3 homozygotes are seldom detected in East Asian populations [5] . CYP2C9*3 has the lowest metabolic activity in vitro, while CYP2C9*2 has an intermediate enzyme activity, and CYP2C9*1 has the highest activity [6] .…”

Section: Introductionmentioning

confidence: 92%

“…The frequencies of CYP2C9 alleles vary between populations, information that is useful for clinical pharmacotherapy. The frequencies of CYP2C9 alleles and genotypes in the Korean population have been calculated [5,[7][8][9] , however, there are significant discrepancies in the reported CYP2C9*3 frequencies. Thus, we measured the CYP2C9 allele and genotype frequencies in a large Korean cohort, where we Frequency of CYP2C9 alleles in Koreans and their effects on losartan pharmacokinetics Jung-woo BAE 1, 3, # , Chang-ik CHOI 1, # , Mi-jeong KIM…”

Section: Introductionmentioning

confidence: 99%

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Frequency of CYP2C9 alleles in Koreans and their effects on losartan pharmacokinetics

et al. 2011

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Aim: CYP2C9 enzyme metabolizes numerous clinically important drugs. The aim of this study is to investigate the frequencies of CYP2C9 genotypes and the effects of selected alleles on losartan pharmacokinetics in a large sample of the Korean population. Methods: The CYP2C9 gene was genotyped in 1796 healthy Korean subjects. CYP2C9 alleles (CYP2C9*1, *2, *3, and *13 alleles) were measured using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay and direct sequencing assay. The enzymatic activity of each CYP2C9 genotype was evaluated using losartan as the substrate. Results: The frequencies of CYP2C9*1, *3, and *13 allele were 0.952 (95% confidence interval 0.945-0.959), 0.044 (95% CI 0.037-0.051), and 0.005 (95% CI 0.003-0.007), respectively. The frequencies of the CYP2C9*1/*1, *1/*3, *1/*13, and *3/*3 genotypes were 0.904 (95% CI 0.890-0.918), 0.085 (95% CI 0.072-0.098), 0.009 (95% CI 0.005-0.013), and 0.001 (95% CI 0.000-0.002), respectively. In the pharmacokinetics studies, the AUC 0-∞ of losartan in CYP2C9*3/*3 subject was 1.42-fold larger than that in CYP2C9*1/*1 subjects, and the AUC 0-∞ of E-3174, a more active metabolite of losartan, in CYP2C9*3/*3 subject was only 12% of that in CYP2C9*1/*1 subjects. Conclusion:The results confirmed the frequencies of CYP2C9 genotypes in a large cohort of Koreans, and detected the CYP2C9*3/*3 genotype. CYP2C9*3/*3 subjects metabolized much less losartan into E-3174 than CYP2C9*1/*1 subjects.

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Distribution of CYP2C913* allele in the Chinese Han and the long‐range haplotype containing CYP2C913* and CYP2C192*

Si¹,

Wang

Zhang

et al. 2012

Biopharm & Drug Disp

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Cytochrome P450 2C9 (CYP2C9) and CYP2C19, located in tandem on chromosome 10q23-24, are known as genetically polymorphic. CYP2C9*13 is an important CYP2C9 variant in Asian populations, and is correlated with the reduced plasma clearance of some clinically important drugs. In this research, the allele frequency of CYP2C9*13 was determined to be 0.42% (95% CI of 0.17% to 0.86%) in 839 Chinese Han, male subjects. All detected subjects with CYP2C9*13 carry the CYP2C19*2 allele, too. Sequencing results infer the CYP2C9*13 haplotype, which contains eight linked SNPs, originates from the CYP2C9*1B haplotype group. CYP2C9*1B has been reported to be linked with CYP2C19*2. These indicate a long-range haplotype containing the CYP2C9*13 and CYP2C19*2 mutation, which means most CYP2C9*13 carriers will carry the CYP2C19*2 allele and the six SNPs of the CYP2C9*1B haplotype group, and may have more reduced intrinsic clearance of drugs such as phenytoin, tolbutamide and chlorpropamide that are metabolized by both CYP2C9 and CYP2C19.

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Allele and genotype frequencies of CYP2C9 in a Korean population

Cited by 82 publications

References 21 publications

Substrate-Dependent Functional Alterations of Seven CYP2C9 Variants Found in Japanese Subjects

Substrate-Dependent Functional Alterations of Seven CYP2C9 Variants Found in Japanese Subjects

Frequency of CYP2C9 alleles in Koreans and their effects on losartan pharmacokinetics

Distribution of CYP2C913* allele in the Chinese Han and the long‐range haplotype containing CYP2C913* and CYP2C192*

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Allele and genotype frequencies of CYP2C9 in a Korean population

Cited by 82 publications

References 21 publications

Substrate-Dependent Functional Alterations of Seven CYP2C9 Variants Found in Japanese Subjects

Substrate-Dependent Functional Alterations of Seven CYP2C9 Variants Found in Japanese Subjects

Frequency of CYP2C9 alleles in Koreans and their effects on losartan pharmacokinetics

Distribution of CYP2C9*13 allele in the Chinese Han and the long‐range haplotype containing CYP2C9*13 and CYP2C19*2

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Distribution of CYP2C913* allele in the Chinese Han and the long‐range haplotype containing CYP2C913* and CYP2C192*