Close Association of UGT1A9 IVS1+399C&gt;T with UGT1A1*28, *6, or *60 Haplotype and Its Apparent Influence on 7-Ethyl-10-hydroxycamptothecin (SN-38) Glucuronidation in Japanese

Saito, Yoshiro; Sai, Kimie; Maekawa, Keiko; Kaniwa, Nahoko; Shirao, Kuniaki; Hamaguchi, Tetsuya; Yamamoto, Noboru; Kunitoh, Hideo; Ohe, Yuichiro; Yamada, Yasuhide; Tamura, Tomohide; Yoshida, Teruhiko; Minami, Hironobu; Ohtsu, Atsushi; Matsumura, Yasuhiro; Saijo, Nagahiro; Sawada, Jun Ichi

doi:10.1124/dmd.108.024208

Cited by 24 publications

(17 citation statements)

References 16 publications

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“…The allele frequencies of CYP2B6 G516T and UGT1A9 I399C>T mutations identified in our study were 23% and 62%, respectively. These frequencies are similar to past reports of approximately 20% and 64% of the allele frequencies of Japanese past reports and UGT1A9 I399C>T mutations 9) , respectively. In our study, no significant differences were found between genetic polymorphisms and waking times after propofol anesthesia.…”

Section: Discussionsupporting

confidence: 79%

“…Propofol is metabolized by its hydroxylation by CYP2B6 and by its glucuronidation by UGT1A9, resulting in propofol changing into a conjugated compound that has no anesthetic activity and is excreted in urine, as with other metabolites 7) . Genetic polymorphisms in CYP2B6 and UGT1A9 have been reported, along with their allele frequency in the Japanese population [8][9][10] . Several studies have shown that the allele frequency of the G516T mutation of CYP2B6 was approximately 20%, and the variation among genetic polymorphisms decreased the enzyme activity of CYP2B6 8) [10][11][12] .…”

Section: Introductionmentioning

confidence: 99%

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Effects of Genetic Polymorphism of CYP2B6 and UGT1A9 and Sex Differences on Pharmacokinetics of Propofol

Kobayashi

Yokozuka

Miyakawa

et al. 2015

J St. Marianna Univ

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Background: Genetic polymorphisms of metabolic enzymes, as well as a patient's sex, age, and individual susceptibility, affect the pharmacokinetics of propofol. Several reports show that polymorphisms of metabolic enzymes of propofol affect loss of consciousness during propofol anesthesia. We investigated whether genetic polymorphisms of the liver cytochrome P450 2B6 (CYP2B6), the main metabolic enzyme for propofol, and UDP-glucuronosyltransferase 1A9 (UGT1A9), as well as sex differences, affect the pharmacokinetics of propofol.Methods: Between June 2009 and May 2011, 94 patients (51 males, 43 females) who underwent respiratory surgery with total intravenous anesthesia were examined. Arterial blood samples were collected immediately or 5, 10, 20, 30 and 60 min after the termination of propofol infusion for the determination of the propofol blood concentrations and genetic polymorphisms of CYP2B6 and UGT1A9. We analyzed blood pharmacokinetics of propofol and assessed the association between genetic polymorphisms, sex differences, and blood pharmacokinetics. Stepwise multiple linear regression analysis was used to detect important factors of pharmacokinetics of propofol.Results: Although C 0 (the blood concentrations of propofol immediately after the termination of propofol infusion) rose for the T/T mutation in CYP2B6, there were no significant differences in changes of blood propofol concentrations after the termination of drug infusion and in waking times for both genetic polymorphisms. C 0 was significantly higher in females than in males (1.7: 1.4 μg/mL, female: male, P=0.015) and the rate of decline in the blood propofol concentration from C 0 to C 5 was faster in females than in males (67: 60%, P=0.015). Stepwise multiple regression analysis revealed that sex (B = 0.32, P = 0.01) was a contributor to C 0 (R = 0.27, P = 0.01).Conclusions: We suggest that differences between females and males for C 0 and the rate of decline in the blood propofol concentration may cause individual differences in both sensitivity and recovery of consciousness from propofol anesthesia. We conclude that polymorphisms of CYP2B6, but not UGT1A, and sex differences affect the pharmacokinetics of propofol.

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Section: Discussionsupporting

confidence: 79%

Section: Introductionmentioning

confidence: 99%

Effects of Genetic Polymorphism of CYP2B6 and UGT1A9 and Sex Differences on Pharmacokinetics of Propofol

Kobayashi

Yokozuka

Miyakawa

et al. 2015

J St. Marianna Univ

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“…As expected, the relative frequencies for these alleles are intermediate in the admixed samples, and the variants are present in frequencies that are proportional to the relative admixture proportions. In the case of UGT1A1 , the frequencies of variants that have been associated with irinotecan response (−3156G>A/−349C>T and UGT1A1*60 ) [32], [33], [34], [35] are also higher in European than Native American and West African populations. The consistent higher frequencies of the functional CYP2D6 and UGT1A1 alleles/haplotypes observed in Europeans vs. the other two populations are probably the result of ascertainment bias, because most of the studies exploring variants with potentially functional effects have been carried out in European populations.…”

Section: Resultsmentioning

confidence: 98%

Exploring the Distribution of Genetic Markers of Pharmacogenomics Relevance in Brazilian and Mexican Populations

et al. 2014

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Studies of pharmacogenomics-related traits are increasingly being performed to identify loci that affect either drug response or susceptibility to adverse drug reactions. However, the effect of the polymorphisms can differ in magnitude or be absent depending on the population being assessed. We used the Affymetrix Drug Metabolizing Enzymes and Transporters (DMET) Plus array to characterize the distribution of polymorphisms of pharmacogenetics and pharmacogenomics (PGx) relevance in two samples from the most populous Latin American countries, Brazil and Mexico. The sample from Brazil included 268 individuals from the southeastern state of Rio de Janeiro, and was stratified into census categories. The sample from Mexico comprised 45 Native American Zapotecas and 224 self-identified Mestizo individuals from 5 states located in geographically distant regions in Mexico. We evaluated the admixture proportions in the Brazilian and Mexican samples using a panel of Ancestry Informative Markers extracted from the DMET array, which was validated with genome-wide data. A substantial variation in ancestral proportions across census categories in Brazil, and geographic regions in Mexico was identified. We evaluated the extent of genetic differentiation (measured as FST values) of the genetic markers of the DMET Plus array between the relevant parental populations. Although the average levels of genetic differentiation are low, there is a long tail of markers showing large frequency differences, including markers located in genes belonging to the Cytochrome P450, Solute Carrier (SLC) and UDP-glucuronyltransferase (UGT) families as well as other genes of PGx relevance such as ABCC8, ADH1A, CHST3, PON1, PPARD, PPARG, and VKORC1. We show how differences in admixture history may have an important impact in the distribution of allele and genotype frequencies at the population level.

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“…Moreover, UGT1A9 Ϫ 118T 9 >T 10 and 1399C>T genetic variations were found in high linkage disequilibrium in the present study ( Fig. 3 ) and among Asians, but not Caucasians ( 29,30 ).…”

Section: Discussionmentioning

confidence: 68%

Determination of major UDP-glucuronosyltransferase enzymes and their genotypes responsible for 20-HETE glucuronidation

Jarrar

Cha

Seo

et al. 2014

Journal of Lipid Research

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Close Association of UGT1A9 IVS1+399C>T with *UGT1A1**28, 6, or 60 Haplotype and Its Apparent Influence on 7-Ethyl-10-hydroxycamptothecin (SN-38) Glucuronidation in Japanese

Cited by 24 publications

References 16 publications

Effects of Genetic Polymorphism of CYP2B6 and UGT1A9 and Sex Differences on Pharmacokinetics of Propofol

Effects of Genetic Polymorphism of CYP2B6 and UGT1A9 and Sex Differences on Pharmacokinetics of Propofol

Exploring the Distribution of Genetic Markers of Pharmacogenomics Relevance in Brazilian and Mexican Populations

Determination of major UDP-glucuronosyltransferase enzymes and their genotypes responsible for 20-HETE glucuronidation

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