ライフサイエンスコーパス: CYP2C19

1 hydroxylase (6% of the activity of wild-type CYP2C19).

2 individuals overall (2% in CYP2D6 and 20% in CYP2C19).

3 ->T genotype and reduced-function alleles of CYP2C19.

4 y examines the transcriptional regulation of CYP2C19.

5 requirement with functional consequences to CYP2C19.

6 , statins with SLCO1B1, and clopidogrel with CYP2C19.

7 assess expression and splicing of CYP2C9 and CYP2C19.

8 nd -1930, which are also highly conserved in CYP2C19.

9 al analogues with inhibitory potency against CYP2C19.

10 requires cytochrome P450s (CYPs), including CYP2C19.

11 and assessed for inhibitory activity against CYP2C19.

12 iting various hepatic CYP450 enzymes, mainly CYP2C19.

13 ity was associated with the gain-of-function CYP2C19*17 allele (adjusted HR for *1/*17 versus *1/*1:

14 R for hetero- and homozygote carriers of the CYP2C19*17 allele were 1.02 (CI 0.71-1.46) and 0.57 (CI

15 ficantly more common among black carriers of CYP2C19*17 or CYP1A2*1C.

16 patients homozygous for CYP2B6*5 (n = 3) or CYP2C19*2 (n = 4) had a higher probability of reaching E

17 clopidogrel response is not explained by the CYP2C19*2 allele (the most frequent loss-of-function all

18 ong whites, carriers of the loss-of-function CYP2C19*2 allele had significantly increased 1-year mort

19 iable external factors, the influence of the CYP2C19*2 allele is intrinsically constant.

20 For the CYP2C19*2 allele, the HR was 1.05 (CI 0.78-1.42) and 0.7

21 The relation between CYP2C19*2 genotype and platelet aggregation was replicat

22 y were extended by examining the relation of CYP2C19*2 genotype to platelet function and cardiovascul

23 CYP2C19*2 genotype was associated with diminished platel

24 o were either heterozygous or homozygous for CYP2C19*2 had a significantly lower risk of developing p

25 Independently, in post hoc analyses, CYP2C19*2 has been associated with worse clinical outcom

26 nance dose of clopidogrel to 225 mg daily in CYP2C19*2 heterozygotes achieved levels of platelet reac

27 With 75 mg daily, CYP2C19*2 heterozygotes had significantly higher on-trea

28 225 mg daily, reduced platelet reactivity in CYP2C19*2 heterozygotes to levels achieved with standard

29 Whereas 52% of CYP2C19*2 heterozygotes were nonresponders (>/=230 PRU)

30 Among CYP2C19*2 heterozygotes, doses up to 300 mg daily signif

31 75-mg dose in noncarriers; in contrast, for CYP2C19*2 homozygotes, doses as high as 300 mg daily did

32 In CYP2C19*2 homozygotes, even with 300 mg daily of clopido

33 In total, 247 noncarriers of a CYP2C19*2 loss-of-function allele were to receive 75 and

34 clopidogrel and prasugrel in the 18 (56.3%) CYP2C19*2 noncarriers (HTPR in 12.5% versus 0, P=0.274),

35 gh-dose clopidogrel can address HTPR only in CYP2C19*2 noncarriers.

36 CYP2C19*2 or *19 alleles did not influence DFS.

37 notypes and enrolled 103 patients who lacked CYP2C19*2 or *3 loss-of-function allele to minimize the

38 In the genotype-guided group, carriers of CYP2C19*2 or CYP2C19*3 loss-of-function alleles received

39 ompared with known predictors, including the CYP2C19*2 polymorphism, IPC may become the preferred pre

40 Furthermore, patients with the CYP2C19*2 variant were more likely (20.9% vs 10.0%) to h

41 as in strong linkage disequilibrium with the CYP2C19*2 variant, and was associated with diminished cl

42 CYP2C19*2 was significantly associated with OTR at 12 to

43 frequencies of the variant alleles CYP2B6*5, CYP2C19*2, CYP2C9*2, and CYP3A5*3 were 12.1%, 25.0%, 4.0

44 otype-guided group, carriers of CYP2C19*2 or CYP2C19*3 loss-of-function alleles received ticagrelor o

45 d with the polymorphisms CYP2B6 516G-->T and CYP2C19 681G-->A, respectively.

46 failure was associated with the polymorphism CYP2C19 681G-->A.

47 spensed medications were CYP2C9, CYP2D6, and CYP2C19 (9197.0 drugs [95% CI, 9167.7-9226.3 drugs], 873

48 Genetic polymorphisms of CYP2C19, a PPI metabolizer may also affect eradication.

49 essential for the stimulation of CYP2E1 and CYP2C19 activities and that the phospholipid composition

50 vention, carriage of even 1 reduced-function CYP2C19 allele appears to be associated with a significa

51 at 30 days attributable to reduced-function CYP2C19 allele carriage was 5.2% in the patients randoml

52 likely to intensify antiplatelet therapy in CYP2C19 allele carriers, but only 20% of poor metabolize

53 clopidogrel, carriers of a reduced-function CYP2C19 allele had significantly lower levels of the act

54 re noncarriers, 26.3% had 1 reduced-function CYP2C19 allele, and 2.2% had 2 reduced-function CYP2C19

55 t on factors that decrease (reduced-function CYP2C19 allele; omeprazole) or increase (cigarette smoki

56 th clopidogrel, carriers of reduced-function CYP2C19 alleles have significantly lower levels of activ

57 Carriers of 1 and 2 reduced-function CYP2C19 alleles were significantly more likely to displa

58 5% CI, 1.24-2.50; P = .002) reduced-function CYP2C19 alleles, as compared with noncarriers.

59 2C19 allele, and 2.2% had 2 reduced-function CYP2C19 alleles.

60 idence supports guiding therapy based on the CYP2C19 allelic variants in patients with an indication

61 throughput sequencing to assay mutations in CYP2C19 and ABCB1, the two genes genetically linked to r

62 Decreased genotype-predicted CYP2C19 and CYP1A2 activities were associated with highe

63 actionability was based on the prevalence of CYP2C19 and CYP2D6 phenotypes, including CYP2D6 allele-s

64 uble mutation stimulated these activities of CYP2C19 and CYP2E1 equivalent to wild-type b(5).

65 Neither antibiotic resistance nor CYP2C19 and CYP3A5 rapid metabolizer status was associat

66 Genotypic resistance was identified and CYP2C19 and CYP3A5 were studied.

67 trate recognition sites (SRSs) with those of CYP2C19 and mutating individual residues by site-directe

68 ) enhances the activities of CYP3A4, CYP2A6, CYP2C19, and CYP17A1 but not that of CYP2E1 or CYP2D6, s

69 Lower levels of CYP2C18, CYP2C19, and CYP3A5 were also detected while CYP1A2, 2A6

70 Cytochrome P450 (CYP)2C9 and CYP2C19 are important human enzymes that metabolize ther

71 rcutaneous intervention, when both ABCB1 and CYP2C19 are taken into account, nearly half of the popul

72 Testing for mutations in CYP2C19, as recommended by the FDA, only correctly predi

73 enes) were investigated per individual, with CYP2C19 being the most frequently examined; genotypes in

74 such as rifampicin and dexamethasone induce CYP2C19 both in vivo in humans and in vitro in human hep

75 tion activity with a K(M) similar to that of CYP2C19 but a 3-fold lower K(cat).

76 CYP2C19, but not PON1 or ABCB1, is a significant determi

77 65G double mutation also failed to stimulate CYP2C19-catalyzed (S)-mephenytoin 4-hydroxylation, where

78 and was selective in regard to inhibition of CYP2C19-catalyzed (S)-mephenytoin hydroxylation in human

79 suggest that these receptors may up-regulate CYP2C19 constitutively and possibly its response to drug

80 tion allele for any of the CYP genes tested (CYP2C19, CYP2C9, CYP2B6, CYP3A5, and CYP1A2).

81 /or multiplex genotyping of 6 pharmacogenes (CYP2C19, CYP2C9, CYP2D6, CYP3A5, VKORC1, and TPMT) that

82 hisms on chromosome 10q24 within the CYP2C18-CYP2C19-CYP2C9-CYP2C8 cluster were associated with dimin

83 Human CYP450 proteins CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 are the major drug-metabolizi

84 epatic CYP enzymes including CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 and the crucial steroidogeni

85 on of alpha-thujone by human CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 occurs with up to 80

86 tional P450 enzymes (CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A5).

87 th only three pharmacokinetic pharmacogenes (CYP2C19, CYP2D6, SLCO1B1).

88 w and meta-analysis, the association between CYP2C19/CYP2D6 genotype and drug levels of several psych

89 iated, P450 isoforms CYP3A4, CYP2D6, CYP2C9, CYP2C19, CYP2E1, and CYP1A2 are responsible for the oxid

90 Polymorphisms in CYP2B6, CYP2C19, CYP3A4, CYP3A5, and MDR1 were characterized.

91 or control of known disease, polymorphisms (CYP2C19, CYP3A5, ABCB1, PON1), noncompliance, co-medicat

92 Common genetic variation in CYP2C19 (cytochrome P450, family 2, subfamily C, polypep

93 Likewise, Bzbr-based CoMFA models of CYP2C19 demonstrated no clear preference for any one lig

94 cogene-NAFLD severity associations including CYP2C19 downregulation.

95 We chose to validate CYP2C19 due to its actionability in drug prescribing.

96 hes for drugs sensitive to metabolism by the CYP2C19 enzyme.

97 (n = 160, age 18 to 55 years, homozygous for CYP2C19 extensive metabolizer genotype, confined, standa

98 ts (n = 160; ages 20 to 53 years; homozygous CYP2C19 extensive metabolizer genotype; no nicotine for

99 lor or prasugrel, which are not dependent on CYP2C19 for activation, has been recommended but can res

100 xon inclusion event between exons 6 and 7 in CYP2C19 for carriers of rs7906871.

101 o acids determining the specificity of human CYP2C19 for S-mephenytoin 4'-hydroxylation, we construct

102 Certain alleles of the CYP2C19 gene are associated with higher platelet reactiv

103 Variants in the CYP2C19 gene influence the pharmacologic and clinical re

104 ytes showed induction of both the CYP2C9 and CYP2C19 genes by tert-butylhydroquinone (tBHQ).

105 ent type (drug-eluting or bare metal stent), CYP2C19 genetic status, loading dose of aspirin, dose of

106 er a P2Y(12) inhibitor on the basis of early CYP2C19 genetic testing (genotype-guided group) or stand

107 Such patients can be identified by CYP2C19 genetic testing and can be treated with alternat

108 The evidence to date supports CYP2C19 genetic testing before oral P2Y12 inhibitors are

109 Our findings do not support routine CYP2C19 genetic testing in this population.

110 We sought to assess the impact of CYP2C19 genetic testing on prescribing patterns for anti

111 index, chronic kidney disease, diabetes, and CYP2C19 genetic variants) score >=10 predicts reduced cl

112 ith HTPR and explore the interaction between CYP2C19 genotype and both drugs.

113 s (EM) or reduced metabolizers (RM) based on CYP2C19 genotype and evaluated ischemic outcomes and pla

114 However, the relationship of CYP2C19 genotype and outcomes in medically managed patie

115 CYP2C19 genotype data was available for 2 423 patients a

116 Meta-analysis of the CYP2C19 genotype effect was stratified by the predominan

117 This study sought to assess the effect of CYP2C19 genotype on ischemic outcomes in patients with A

118 identified by platelet function testing, the CYP2C19 genotype provides limited incremental informatio

119 the study was to determine whether returning CYP2C19 genotype results along with genotype-guided phar

120 in breast cancer patients and, consequently, CYP2C19 genotype status should not be included in clinic

121 bolite levels, cytochrome P450 1A2 activity, CYP2C19 genotype, and safety parameters were determined.

122 est its pharmacologic effect varies based on CYP2C19 genotype, but there is uncertainty regarding the

123 useful as a scientific foundation for CYP2D6/CYP2C19 genotype-based dosing recommendations.

124 In patients undergoing primary PCI, a CYP2C19 genotype-guided strategy for selection of oral P

125 ave been proposed to influence the effect of CYP2C19 genotype.

126 ed by therapy with prasugrel irrespective of CYP2C19 genotype.

127 view and meta-analysis found that CYP2C9 and CYP2C19 genotypes encoding low enzymatic capacity were a

128 ABCB1 3435C-->T and CYP2C19 genotypes were significant, independent predicto

129 e initial TCA dosage was based on CYP2D6 and CYP2C19 genotypes.

130 In a randomized controlled trial of clinical CYP2C19 genotyping implementation, pharmacogenetic test

131 ion, but the clinical impact of implementing CYP2C19 genotyping in a real-world setting is unknown.

132 he most common implementation in practice is CYP2C19 genotyping to predict clopidogrel response and a

133 Clinical follow-up (until 3 months) and CYP2C19 genotyping was performed in all patients.

134 A total of 4,335 patients who underwent PCI, CYP2C19 genotyping, and P2Y(12) inhibitor treatment were

135 ts were identified, and 499 (8.3%) underwent CYP2C19 genotyping, of whom 146 (30%) were found to have

136 l who have >/=1 loss of function alleles for CYP2C19 have an increased risk for adverse cardiovascula

137 262 patients), and sertraline hydrochloride (CYP2C19 IM vs NM RoM, 1.38; 95% CI, 1.27-1.51; 3 studies

138 mpounds were docked into a homology model of CYP2C19 in an effort to understand the enzyme-ligand int

139 bolites induces the expression of CYP2C9 and CYP2C19 in human hepatocytes.

140 Our data demonstrate the downregulation of CYP2C19 in NAFLD which supports developing personalized

141 ssing SRSs 1--4 was active (30% of wild-type CYP2C19), indicating that multiple regions are necessary

142 n studies, where CYP3A4, CYP1A2, CYP2C9, and CYP2C19 inductions were achieved following rifampicin tr

143 The data was used to build a CYP2C19 inhibition pharmacophore model for the series.

144 nzbromarone (Bzbr) to create the most potent CYP2C19 inhibitor ever reported.

145 ediate metabolizers, 12% (95% CI, 2%-24%) in CYP2C19 intermediate metabolizers, and 20% (95% CI, 2%-4

146 diate metabolizers, 20% (95% CI, 17%-30%) in CYP2C19 intermediate metabolizers, and 39% (95% CI, 24%-

147 CYP2C19 is an important human drug-metabolizing enzyme t

148 CYP2C19 is involved in the metabolism of 10%-15% of comm

149 ve been intensively studied, but the role of CYP2C19 is less elucidated, and we studied the associati

150 CYP2C19 is selective for the 4'-hydroxylation of S-mephe

151 s of 16 independent studies demonstrate that CYP2C19 is significantly downregulated to 46% in NASH, t

152 Upon identifying inhibitors of CYP2C19, ligand-based design shifted to attenuating the

153 The reported association between CYP2C19 LoF allele carriage and major cardiovascular out

154 e of alternative therapy over clopidogrel in CYP2C19 LOF allele carriers after PCI, regardless of ABC

155 Among CYP2C19 LOF allele carriers, MAE risk appeared lower wit

156 s were identified in secondary analyses of 2 CYP2C19 LoF alleles, stent thrombosis outcomes, and stud

157 nce given that over 50% of Asians carry >/=1 CYP2C19 LoF alleles.

158 The association between carriage of >/=1 CYP2C19 loss-of-function (LoF) allele and major cardiova

159 to sufficiently overcome high reactivity in CYP2C19 loss-of-function (LOF) allele carriers.

160 tratifying by ABCD-GENE score and further by CYP2C19 loss-of-function (LOF) genotype.

161 outine care to determine whether identifying CYP2C19 loss-of-function allele patients prospectively a

162 ctors within 90 days in patients who carried CYP2C19 loss-of-function alleles and received dual antip

163 CYP2C19 loss-of-function alleles impair clopidogrel effe

164 ever, routine clinical use of genotyping for CYP2C19 loss-of-function alleles in patients undergoing

165 et drug prescribing; however, almost half of CYP2C19 loss-of-function carriers continued to receive c

166 rospective rapid point-of-care genotyping of CYP2C19 major alleles (*2, *3, *17) via salivary swab (g

167 hemical inhibitor (tranylcypromine) for this CYP2C19-mediated reaction.

168 nhibitors less metabolized by or that bypass CYP2C19 metabolism were used.

169 ns with proton pump inhibitors predominantly CYP2C19 metabolized, enhanced vs poor metabolizer phenot

170 There was no association between CYP2C19 metabolizer status (EM vs. RM) and the primary c

171 CYP2C19 metabolizer status is not associated with the co

172 ssion with hCAR also up-regulated endogenous CYP2C19 mRNA content in HepG2 cells.

173 morphism by itself and alongside variants in CYP2C19 on cardiovascular outcomes in patients treated w

174 ollowing inclusion criteria: (1) appropriate CYP2C19 or CYP2D6 genotyping was performed, (2) genotype

175 rmed, (2) genotype-based classification into CYP2C19 or CYP2D6 NM, IM, and PM categories was possible

176 g, 65% had potentially actionable CYP2D6 and CYP2C19 phenotypes, and phenotype assignment was impacte

177 udies; 1492 patients), escitalopram oxalate (CYP2C19 PM vs NM, RoM, 2.63; 95% CI, 2.40-2.89; 4 studie

178 e to support a clinically meaningful role of CYP2C19 polymorphisms and response to tamoxifen in breas

179 According to the CYP2C19 polymorphisms, 79.5% of the RUT-positive patient

180 rom 11 countries; the vast majority analyzed CYP2C19 polymorphisms.

181 t reactivity including cytochrome P450 2C19 (CYP2C19) polymorphisms, age, body mass index, diabetes,

182 tioners to consider alternative treatment in CYP2C19 poor metabolizers who might receive clopidogrel

183 te metabolizers, and 20% (95% CI, 2%-41%) in CYP2C19 poor metabolizers; and for carbamazepine, by 12%

184 e metabolizers, and 39% (95% CI, 24%-56%) in CYP2C19 poor metabolizers; for valproate, by 12% (95% CI

185 However, PPIs may inhibit CYP2C19, potentially reducing the effectiveness of clopi

186 ceptor binding sites (CAR/PXR and GR) in the CYP2C19 promoter and to suggest that these receptors may

187 Dexamethasone activated the -2.7-kb CYP2C19 promoter constructs in HepG2 cells only in the p

188 in HepG2 cells up-regulated transcription of CYP2C19 promoter constructs, whereas mutation of the -18

189 mCAR-mediated constitutive activation of the CYP2C19 promoter in HepG2 cells, whereas the potent mCAR

190 Analysis of the CYP2C19 promoter revealed a single constitutive androsta

191 d with clopidogrel, carriers of at least one CYP2C19 reduced-function allele (approximately 30% of th

192 patients taking clopidogrel who were either CYP2C19 reduced-function allele carriers, ABCB1 3435 TT

193 nd 2 (HR, 3.97; 95% CI, 1.75-9.02; P = .001) CYP2C19 reduced-function alleles, as compared with nonca

194 etabolized by cytochrome P-450 (CYP) 2B6 and CYP2C19, respectively, with some involvement by CYP3A.

195 rs, azathioprine (NUDT15/TPMT), clopidogrel (CYP2C19), statins (ABCG2/CYP2C9/SLCO1B1), and NSAIDs (CY

196 on DGIs included proton pump inhibitors with CYP2C19, statins with SLCO1B1, and clopidogrel with CYP2

197 patient had a heterozygous null mutation in CYP2C19 suggesting probable clopidogrel resistance, seve

198 lizing enzymes GSTT1, GSTM1, CYP1A1, CYP2D6, CYP2C19, SULT1A1, and NQO1 were previously determined fo

199 rvention prescribed clopidogrel were offered CYP2C19 testing.

200 explained by genetic polymorphisms encoding CYP2C19, the hepatic enzyme involved in biotransformatio

201 hydroxylation reaction as performed by human CYP2C19, the major human omeprazole-metabolizing P450 en

202 There was no association between CYP2C19 variants and eradication failure if proton pump

203 Though CYP2C19 was known to prefer neutral substrates, the exte

204 CLA resistance and the polymorphisms of CYP2C19 were determined on DNA extracted from gastric bi

205 were also found in the 3'-UTRs of CYP2C9 and CYP2C19, which suggested that the same miRNAs could regu

206 agrelor, and genotyping for polymorphisms of CYP2C19 with carriers of loss-of-function alleles receiv

207 atures enabling analogues of Bzbr to bind to CYP2C19 with high affinity are low acidity (high pK(a) o