Population Differences in Major Functional Polymorphisms of Pharmacokinetics/pharmacodynamics-related Genes in Eastern Asians and Europeans: Implications in the Clinical Trials for Novel Drug Development

Kurose, Kouichi; Sugiyama, Emiko; Saito, Yoshiro

doi:10.2133/dmpk.dmpk-11-rv-111

Cited by 209 publications

(222 citation statements)

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“…The minor *3 allele frequency has been described in the African population (1.8%) and the major allele in the Southern European (8.6%) population (Kurose et al, 2012). Both the CYP2C9*2 and *3 allele frequencies were similar to that reported by Llerena et al, (2004) in a Mexican-American population (9 and 5%, respectively).…”

Section: Resultssupporting

confidence: 67%

“…The CYP2C19*2 allele had a frequency of 7.9%, similar (P > 0.08) to Mexican-American, West Asian, and Southern and Eastern European populations (Luo et al, 2006;Kurose et al, 2012). The CYP2C19*2 allele frequency was statistically different from Western and Northern European; Southern, South-Eastern, and Southern Asian; Caucasian; and African populations (P ≤ 0.042), whose frequencies range from 14 to 29.8% (Kurose et al, 2012).…”

Section: Resultsmentioning

confidence: 75%

“…The CYP2C19*2 allele frequency was statistically different from Western and Northern European; Southern, South-Eastern, and Southern Asian; Caucasian; and African populations (P ≤ 0.042), whose frequencies range from 14 to 29.8% (Kurose et al, 2012).…”

Section: Resultsmentioning

confidence: 76%

“…Correlation analysis of the clinical variables contrasted with dose of acenocoumarol. (Kurose et al, 2012). The minor/major *2 allele frequency is described in the Eastern Asian (<0.1%) and Southern European (14.3%) populations, respectively (Kurose et al, 2012).…”

Section: Resultsmentioning

confidence: 96%

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Genetic contribution of CYP2C9, CYP2C19, and APOE variants in acenocoumarol response

et al. 2013

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ABSTRACT. Oral anticoagulants of the coumarin type have an inconveniently narrow therapeutic window, making their use difficult. In Mexico, genetic variables that participate in the heterogeneity of the therapeutic response remain poorly investigated. With the focus on warfarin, extensive pharmacogenomic studies have been performed, including those on the CYP450 family and APOE. The objective of this study was to determine the contribution of CYP2C9, CYP2C19, and APOE polymorphisms to the variations in response to the doses of acenocoumarol, which is the main anticoagulant prescribed to the Mexican population. The polymerase chain reaction-restriction fragment length polymorphism method was applied to identify *2 and *3 of CYP2C9, *2 of CYP2C19, and APOE variants. The genetic distribution of every polymorphism tested showed high variability when compared with other populations worldwide. Our results showed statistical differences only in the CYP2C19 gene between the *1*1 and *1*2 groups, with effective acenocoumarol doses of 2.56 ± 1.34 mg/day vs 1.35 ± 0.84 mg/day (P = 0.005), respectively. Multiple regression analysis, including patient age and both the CYP2C9 and CYP2C19 genes, showed that these variables explained more than 20% of the dose variations. This is the first report in Mexico searching for the relationship between CYP450 and APOE polymorphisms and the dose requirements of acenocoumarol. Our results suggest that, in the Mexican population, CYP2C19 is more involved in acenocoumarol metabolism than CYP2C9 and APOE. Besides considering the age factor, pharmacogenetic testing for CYP2C19*2 before initiating acenocoumarol treatment could lead to a safer anticoagulation therapy in Mexican patients.

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Section: Resultssupporting

confidence: 67%

Section: Resultsmentioning

confidence: 75%

Section: Resultsmentioning

confidence: 76%

Section: Resultsmentioning

confidence: 96%

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Genetic contribution of CYP2C9, CYP2C19, and APOE variants in acenocoumarol response

et al. 2013

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“…Polymorphisms within the amino acid sequences of the majority of phase I and phase II drug-metabolizing enzymes (DMEs), as well as transporters, contribute to the clinical efficacy of drugs (Kurose et al, 2012). Genomewide association studies focusing on the response to drugs, which include analyses of candidate genes encoding DMEs, reveal the endogenous effects of genetic variations that affect drug metabolism and drug responses (Low et al, 2014;Sim et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Whole exome sequencing detects variants of genes that mediate response to anticancer drugs

et al. 2017

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-Certain interindividual differences affecting the efficacy of drug treatment and adverse drug reactions are caused by genetic variants, and their phenotypic effects differ among ethnic groups. In this study, we used whole exome sequencing (WES) systematically to identify germline mutations that influence the activities of drug-metabolizing enzymes, as well as that of a transporter. We analyzed DNA isolated from blood samples from 2,042 Japanese patients with diverse cancers. We identified sequence variants of CYP2B6 (rs3745274), CYP2C9 (rs1057910), CYP2C19 (rs4986893), CYP2C19 (rs4244285), TPMT (rs1142345), NAT2 (rs1799930), NAT2 (rs1799931), UGT1A1 (rs4148323), COMT (rs4680), ABCB1 (rs1045642), and CDA (rs60369023). Wider application of WES will help to determine the effects of mutations on the activities of proteins encoded by drug response genes, and the information gained will accelerate the development of personalized therapies for patients with cancer. Moreover, this knowledge may provide clues for preventing cancer before the onset of symptoms.

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Hypoglycemia After Antimicrobial Drug Prescription for Older Patients Using Sulfonylureas

Parekh¹,

Raji

Lin

et al. 2014

JAMA Intern Med

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IMPORTANCE Certain antimicrobial drugs interact with sulfonylureas to increase the risk of hypoglycemia.OBJECTIVE To determine the risk of hypoglycemia and associated costs in older patients prescribed glipizide or glyburide who fill a prescription for an antimicrobial drug. DESIGN, SETTING, AND PARTICIPANTSThis was a retrospective cohort study of Texas Medicare claims from 2006 to 2009 for patients 66 years or older who were prescribed glipizide or glyburide and who also filled a prescription for 1 of the 16 antimicrobials most commonly prescribed for this population.METHODS We assessed hypoglycemia events and associated Medicare costs in patients prescribed 1 of 7 antimicrobial agents thought to interact with sulfonylureas, using noninteracting antimicrobials as a comparison. We used a repeated measure logistic regression, controlling for age, sex, ethnicity, Medicaid eligibility, comorbidity, prior emergency department visits for hypoglycemia, prior hospitalizations for any cause, nursing home residence, and indication for the antimicrobial. We estimated odds of hypoglycemia, number needed to harm, deaths during hospitalization for hypoglycemia, and Medicare costs for hypoglycemia treatment. MAIN OUTCOMES AND MEASURESAny hospitalization or emergency department visit owing to hypoglycemia within 14 days of antimicrobial exposure. RESULTSIn multivariable analyses controlling for patient characteristics and indication for antimicrobial drug use, clarithromycin (odds ratio [OR], 3.96 [95% CI, 2.42-6.49]), levofloxacin (OR, 2.60 [95% CI, 2.18-3.10]), sulfamethoxazole-trimethoprim (OR, 2.56 [95% CI, 2.12-3.10]), metronidazole (OR, 2.11 [95% CI,), and ciprofloxacin (OR, 1.62 [95% CI, 1.33-1.97]) were associated with higher rates of hypoglycemia compared with a panel of noninteracting antimicrobials. The number needed to harm ranged from 71 for clarithromycin to 334 for ciprofloxacin. Patient factors associated with hypoglycemia included older age, female sex, black or Hispanic race/ethnicity, higher comorbidity, and prior hypoglycemic episode. In 2009, 28.3% of patients prescribed a sulfonylurea filled a prescription for 1 of these 5 antimicrobials, which were associated with 13.2% of all hypoglycemia events in patients taking sulfonylureas. The treatment of subsequent hypoglycemia adds $30.54 in additional Medicare costs to each prescription of 1 of those 5 antimicrobials given to patients taking sulfonylureas.CONCLUSIONS AND RELEVANCE Prescription of interacting antimicrobial drugs to patients on sulfonylureas is very common, and is associated with substantial morbidity and increased costs.

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Population Differences in Major Functional Polymorphisms of Pharmacokinetics/pharmacodynamics-related Genes in Eastern Asians and Europeans: Implications in the Clinical Trials for Novel Drug Development

Cited by 209 publications

References 346 publications

Genetic contribution of CYP2C9, CYP2C19, and APOE variants in acenocoumarol response

Genetic contribution of CYP2C9, CYP2C19, and APOE variants in acenocoumarol response

Whole exome sequencing detects variants of genes that mediate response to anticancer drugs

Hypoglycemia After Antimicrobial Drug Prescription for Older Patients Using Sulfonylureas

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