Effect of race and glucuronidation rates on the relationship between nicotine metabolite ratio and nicotine clearance
| Autor: | Peyton Jacob, Evangelia Liakoni, Rachel F. Tyndale, Delia A. Dempsey, Newton Addo, Neal L. Benowitz |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Saliva Metabolite Glucuronidation Urine 030226 pharmacology & pharmacy Nicotine chemistry.chemical_compound 0302 clinical medicine nicotine metabolite ratio Pharmacology & Pharmacy Glucuronosyltransferase General Pharmacology Toxicology and Pharmaceutics 610 Medicine & health Cotinine Genetics (clinical) media_common African Americans Smoking Pharmacology and Pharmaceutical Sciences racial differences Molecular Medicine nicotine clearance Glucuronide medicine.drug medicine.medical_specialty Genotype media_common.quotation_subject Article 03 medical and health sciences Glucuronides Internal medicine Tobacco Genetics medicine Humans cotinine Molecular Biology Tobacco Smoke and Health business.industry Addiction glucuronidation Brain Disorders Black or African American Good Health and Well Being 030104 developmental biology Endocrinology chemistry business |
| Zdroj: | Pharmacogenetics and genomics, vol 31, iss 5 Pharmacogenet Genomics Liakoni, Evangelia; Tyndale, Rachel F; Jacob, Peyton; Dempsey, Delia A; Addo, Newton; Benowitz, Neal L (2021). Effect of race and glucuronidation rates on the relationship between nicotine metabolite ratio and nicotine clearance. Pharmacogenetics and genomics, 31(5), pp. 97-107. Lippincott Williams & Wilkins 10.1097/FPC.0000000000000427 |
| ISSN: | 1744-6872 |
| Popis: | Author(s): Liakoni, Evangelia; Tyndale, Rachel F; Jacob, Peyton; Dempsey, Delia A; Addo, Newton; Benowitz, Neal L | Abstract: ObjectivesTo investigate if the nicotine metabolite ratio (NMR, the ratio of nicotine metabolites 3'-hydroxycotinine/cotinine) is a reliable phenotypic biomarker for nicotine clearance across races, and as a function of differences in the rate of nicotine, cotinine and 3'-hydroxycotinine glucuronidation and UGT genotypes.MethodsParticipants [Caucasians (Whites), African Americans (Blacks) and Asian-Americans (Asians)] received an oral solution of deuterium-labeled nicotine and its metabolite cotinine. Plasma and saliva concentrations of nicotine and cotinine were used to determine oral clearances. Rates of glucuronidation were assessed from urine glucuronide/parent ratios, and UGT2B10 and UGT2B17 genotypes from DNA.ResultsAmong the 227 participants, 96 (42%) were White, 67 (30%) Asian and 64 (28%) Black. Compared to the other two races, Whites had higher nicotine and cotinine total oral clearance, Blacks had lower nicotine and cotinine glucuronidation rates and Asians had lower 3'-hydroxycotinine glucuronidation rates. A strong positive correlation (correlations coefficients 0.77-0.84; P l 0.001) between NMR and nicotine oral clearance was found for all three races, and NMR remained a strong predictor for the nicotine oral clearance while adjusting for race, sex and age. Neither the metabolite glucuronidation ratios nor the UGT genotypes had significant effects on the ability of NMR to predict nicotine oral clearance.ConclusionNMR appears to be a reliable phenotypic biomarker for nicotine clearance across races, glucuronidation phenotypes and genotypes. Racial differences in the relationships between NMR, smoking behaviors and addiction are unlikely to be related to an inadequate estimation of nicotine clearance on the basis of NMR. |
| Databáze: | OpenAIRE |
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