| Worldwide variation in human drug-metabolism enzyme genes CYP2B6 and UGT2B7: implications for HIV/AIDS treatment. | |
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MedLine Citation:
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PMID: 22462748 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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AIM: Hepatic enzymes, CYP2B6 and UGT2B7 play a major role in the metabolism of the widely used antiretroviral drugs efavirenz, nevirapine and zidovudine. In the present study, we provide a view of UGT2B7 haplotype structure, and quantify the genetic diversity and differentiation at both CYP2B6 and UGT2B7 genes on a worldwide scale. MATERIALS & METHODS: We genotyped one intronic and three promoter SNPs, and together with three nonsynonymous SNPs, inferred UGT2B7 alleles in north American (n = 326), west African (n = 133) and Papua New Guinean (n = 142) populations. We also included genotype data for five CYP2B6 and six UGT2B7 SNPs from an additional 12 worldwide populations (n = 629) analyzed in the 1000 Genomes Project. RESULTS: We observed significant differences in certain SNP and allele frequencies of CYP2B6 and UGT2B7 among worldwide populations. Diversity values were higher for UGT2B7 than for CYP2B6, although there was more diversity between populations for CYP2B6. For both genes, most of the genetic variation was observed among individuals within populations, with the Papua New Guinean population showing the highest pairwise differentiation values for CYP2B6, and the Asian and European populations showing higher pairwise differentiation values for UGT2B7. CONCLUSION: These new genetic distinctions provide additional insights for investigating differences in antiretroviral pharmacokinetics and therapy outcomes among ethnically and geographically diverse populations. |
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Authors:
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Jing Li; Vincent Menard; Rebekah L Benish; Richard J Jurevic; Chantal Guillemette; Mark Stoneking; Peter A Zimmerman; Rajeev K Mehlotra |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Pharmacogenomics Volume: 13 ISSN: 1744-8042 ISO Abbreviation: Pharmacogenomics Publication Date: 2012 Apr |
Date Detail:
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Created Date: 2012-04-02 Completed Date: 2012-12-18 Revised Date: 2013-04-08 |
Medline Journal Info:
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Nlm Unique ID: 100897350 Medline TA: Pharmacogenomics Country: England |
Other Details:
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Languages: eng Pagination: 555-70 Citation Subset: IM |
Affiliation:
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Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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African Continental Ancestry Group
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genetics Anti-HIV Agents / pharmacokinetics*, therapeutic use Aryl Hydrocarbon Hydroxylases / genetics* Asian Continental Ancestry Group / genetics European Continental Ancestry Group / genetics Gene Frequency Genotype Glucuronosyltransferase / genetics* HIV Infections / drug therapy*, enzymology, genetics HapMap Project Human Genome Project Humans Oxidoreductases, N-Demethylating / genetics* Papua New Guinea Polymorphism, Single Nucleotide* |
| Grant Support | |
ID/Acronym/Agency:
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1P01DE019759-01/DE/NIDCR NIH HHS; AI36219/AI/NIAID NIH HHS; MOP-42392//Canadian Institutes of Health Research; P01 DE019759/DE/NIDCR NIH HHS; UL1 RR024989/RR/NCRR NIH HHS; UL1RR024989/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Anti-HIV Agents; EC 1.14.14.1/Aryl Hydrocarbon Hydroxylases; EC 1.14.14.1/S-mephenytoin N-demethylase; EC 1.5.-/Oxidoreductases, N-Demethylating; EC 2.4.1.-/UGT2B7 protein, human; EC 2.4.1.17/Glucuronosyltransferase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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