التفاصيل البيبلوغرافية
| العنوان: |
Effect of UGT2B10, UGT2B17, FMO3, and OCT2 genetic variation on nicotine and cotinine pharmacokinetics and smoking in African Americans |
| المؤلفون: |
Taghavi, Taraneh, St.Helen, Gideon, Benowitz, Neal L, Tyndale, Rachel F |
| المصدر: |
Pharmacogenetics and Genomics, vol 27, iss 4 |
| بيانات النشر: |
eScholarship, University of California |
| سنة النشر: |
2017 |
| المجموعة: |
University of California: eScholarship |
| مصطلحات موضوعية: |
Pharmacology and Pharmaceutical Sciences, Biological Sciences, Biomedical and Clinical Sciences, Genetics, Tobacco Smoke and Health, Tobacco, Cancer, Good Health and Well Being, Administration, Intravenous, Black or African American, Cotinine, Genotype, Glucuronosyltransferase, Humans, Minor Histocompatibility Antigens, Mixed Function Oxygenases, Nicotine, Organic Cation Transport Proteins, Organic Cation Transporter 2, Pharmacogenomic Variants, Polymorphism, Single Nucleotide, Smoking, African American, FMO3, glucuronidation, OCT2, pharmacokinetics, UGT2B10 |
| جغرافية الموضوع: |
143 - 154 |
| الوصف: |
ObjectivesNicotine metabolism rates differ considerably among individuals, even after controlling for variation in the major nicotine-metabolizing enzyme, CYP2A6. In this study, the impact of genetic variation in alternative metabolic enzymes and transporters on nicotine and cotinine (COT) pharmacokinetics and smoking was investigated.MethodsWe examined the impact of UGT2B10, UGT2B17, FMO3, NAT1, and OCT2 variation on pharmacokinetics and smoking (total nicotine equivalents and topography) before and after stratifying by CYP2A6 genotype in 60 African American (AA) smokers who received a simultaneous intravenous infusion of deuterium-labeled nicotine and COT.ResultsVariants in UGT2B10 and UGT2B17 were associated with urinary glucuronidation ratios (glucuronide/free substrate). UGT2B10 rs116294140 was associated with significant alterations in COT and modest alterations in nicotine pharmacokinetics. These alterations, however, were not sufficient to change nicotine intake or topography. Neither UGT2B10 rs61750900, UGT2B17*2, FMO3 rs2266782, nor NAT1 rs13253389 altered nicotine or COT pharmacokinetics among all individuals (n=60) or among individuals with reduced CYP2A6 activity (n=23). The organic cation transporter OCT2 rs316019 significantly increased nicotine and COT Cmax (P=0.005, 0.02, respectively) and decreased nicotine clearance (P=0.05). UGT2B10 rs116294140 had no significant impact on the plasma or urinary trans-3'-hydroxycotinine/COT ratio, commonly used as a biomarker of CYP2A6 activity.ConclusionWe found that polymorphisms in genes other than CYP2A6 represent minor sources of variation in nicotine pharmacokinetics, insufficient to alter smoking in AAs. The change in COT pharmacokinetics with UGT2B10 rs116294140 highlights the UGT2B10 gene as a source of variability in COT as a biomarker of tobacco exposure among AA smokers. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
unknown |
| العلاقة: |
qt4df9k4nz; https://escholarship.org/uc/item/4df9k4nzTest |
| الإتاحة: |
https://escholarship.org/uc/item/4df9k4nzTest |
| حقوق: |
CC-BY-NC-SA |
| رقم الانضمام: |
edsbas.AAFF8667 |
| قاعدة البيانات: |
BASE |
