Genotype–phenotype correlation of cytochrome P450 2C9 polymorphism in Indian National Capital Region

Varshney, Ekta; Saha, Nilanjan; Tandon, Monika; Shrivastava, Vikesh; Ali, Shakir

doi:10.1007/s13318-013-0124-2

Cited by 9 publications

(4 citation statements)

References 45 publications

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“…Genetic profiles constitute important factors to infer metabolic phenotypes and CYP2C9 genotypes were sufficient to correctly identify the majority of individuals with impaired CYP2C9 activity [ 29 , 30 ]. Estimation of metabolizer status at the population-scale, requires the aggregation of prevalence data from as many as possible functionally relevant alleles.…”

Section: Discussionmentioning

confidence: 99%

Global distribution of functionally important CYP2C9 alleles and their inferred metabolic consequences

et al. 2023

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Background Genetic variability in the cytochrome P450 CYP2C9 constitutes an important predictor for efficacy and safety of various commonly prescribed drugs, including coumarin anticoagulants, phenytoin and multiple non-steroidal anti-inflammatory drugs (NSAIDs). A global map of CYP2C9 variability and its inferred functional consequences has been lacking. Results Frequencies of eight functionally relevant CYP2C9 alleles (*2, *3, *5, *6, *8, *11, *13 and *14) were analyzed. In total, 108 original articles were identified that included genotype data from a total of 81,662 unrelated individuals across 70 countries and 40 unique ethnic groups. The results revealed that CYP2C9*2 was most abundant in Europe and the Middle East, whereas CYP2C9*3 was the main reason for reduced CYP2C9 activity across South Asia. Our data show extensive variation within superpopulations with up to tenfold differences between geographically adjacent populations in Malaysia, Thailand and Vietnam. Translation of genetic CYP2C9 variability into functional consequences indicates that up to 40% of patients in Southern Europe and the Middle East might benefit from warfarin and phenytoin dose reductions, while 3% of patients in Southern Europe and Israel are recommended to reduce starting doses of NSAIDs. Conclusions This study provides a comprehensive map of the genetic and functional variability of CYP2C9 with high ethnogeographic resolution. The presented data can serve as a useful resource for CYP2C9 allele and phenotype frequencies and might guide the optimization of genotyping strategies, particularly for indigenous and founder populations with distinct genetic profiles.

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Section: Discussionmentioning

confidence: 99%

Global distribution of functionally important CYP2C9 alleles and their inferred metabolic consequences

et al. 2023

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“…18 Homozygotes for *3 allele show only 25% of the activity, while in heterozygotes this is between 40% and 75%, depending on the substrate. 19,20 The allele frequency *2 (rs1799853, 430C>T) is about 6.8%. In our study, the representation of this heterozygous CYP2C9*2 (C/T) allele in children was (19.1%), while the representation of homozygous form (T/T) was 2.1%.…”

Section: Discussionmentioning

confidence: 99%

The Effect of UGT1A9, CYP2B6 and CYP2C9 Genes Polymorphism on Propofol Pharmacokinetics in Children

Pavlovic

Budić

Stoimenov

et al. 2020

PGPM

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This study was conducted to determine the effect of UGT1A9 98T>C, CYP2B6 516G>T and CYP2C9 430C>T genetic polymorphisms on the pharmacokinetics of propofol in children of different sexes and ages who undergone total intravenous anesthesia (ТIVA) and deep sedation during diagnostic and therapeutic procedures. Patients and Methods: The prospective study included 94 children, ASA I-II status, 1 to 17 years of age, who undergone standard anesthetic protocol for TIVA, which implied the continuous use of propofol. Before the administration of propofol, venous blood was sampled to determine the presence of genetic variations in UGT1A9, CYP2B6 and CYP2C9 gene using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). From each patient included in the study blood samples were taken: 10 mins after the induction of anesthesia, immediately before the discontinuation of the propofol infusion, 10 mins after discontinuation of the propofol infusion and 20 mins after discontinuation of the propofol infusion to determine the pharmacokinetics of the drug in the plasma of the subjects The plasma propofol concentration was determined by HPLC analytical technique. Results: UGT1A9 genotype is an independent predictor of the propofol concentration in children immediately after the end of the continuous infusion and 10 mins afterwards. In the carriers of the polymorphic UGT1A9 C allele, the propofol distribution constant was higher. The carriers of the polymorphic CYP2B6 T allele received a significantly lower overall and initial dose of propofol. Unlike polymorphism of the UGT1A9 gene, the tested CYP2C9 and CYP2B6 gene polymorphisms are not independent predictors of the pharmacokinetics of propofol. Conclusion: Further investigations of UGT1A9, CYP2B6 and CYP2C9 and other genes that participate in propofol metabolism as well as detailed analyses of the general conditions, administered therapies and associated diseases could explain the large interindividual variability of propofol metabolism in children.

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“…Thus, the clinical hypotensive activity is predominantly mediated by the active metabolite EXP3174, although losartan itself exhibits good efficacy (Varshney et al. 2013 ). Because of its good anti-hypertension effect, losartan has been one of the anti-hypertension drug most frequently used for the prevention and control of hypertension in the clinic (Yasar et al.…”

Section: Introductionmentioning

confidence: 99%

Effects of Ginkgo leaf tablets on the pharmacokinetics of losartan and its metabolite EXP3174 in rats and its mechanism

Dong

Yuan

et al. 2018

Pharmaceutical Biology

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Context: Ginkgo leaf tablets (GLTs) and losartan are often simultaneously used for the treatment of hypertension in Chinese clinics. However, the herb–drug interaction between GLT and losartan is still unknown.Objective: This study investigates the effects of GLT on the pharmacokinetics of losartan and its metabolite EXP3174 in rats and its potential mechanism.Materials and methods: The pharmacokinetic profiles of losartan and EXP3174 of orally administered losartan (10 mg/kg) with or without GLT pretreatment (80 mg/kg/day for 10 days) in Sprague–Dawley rats were determined. In vitro, the effects of GLT on the metabolic stability of losartan were investigated with rat liver microsomes.Results: The Cmax (1.22 ± 0.25 vs 1.85 ± 0.37 μg/mL) and the AUC(0–t) (6.99 ± 1.05 vs 11.94 ± 1.79 mg·h/L) of losartan increased significantly (p < 0.05) with GLT pretreatment, while the Cmax (1.05 ± 0.19 vs 0.72 ± 0.12 μg/mL) of EXP3174 decreased significantly (p < 0.05) compared to the control. The t1/2 of losartan was prolonged significantly from 3.94 ± 0.62 to 4.75 ± 0.52 h (p < 0.05). The metabolic stability of losartan was increased from 37.4 min to 59.6 min with GLT pretreatment.Discussion and conclusions: The results indicate that GLT might increase the plasma concentration of losartan and decrease the concentration of EXP3174 through inhibiting the metabolism of losartan.

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Genotype–phenotype correlation of cytochrome P450 2C9 polymorphism in Indian National Capital Region

Cited by 9 publications

References 45 publications

Global distribution of functionally important CYP2C9 alleles and their inferred metabolic consequences

Global distribution of functionally important CYP2C9 alleles and their inferred metabolic consequences

<p>The Effect of <em>UGT1A9</em>, <em>CYP2B6</em> and <em>CYP2C9</em> Genes Polymorphism on Propofol Pharmacokinetics in Children</p>

Effects of Ginkgo leaf tablets on the pharmacokinetics of losartan and its metabolite EXP3174 in rats and its mechanism

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