Pharmacogenetic associations with plasma efavirenz concentrations and clinical correlates in a retrospective cohort of Ghanaian HIV-infected patients.
Identifieur interne : 000373 ( PubMed/Curation ); précédent : 000372; suivant : 000374Pharmacogenetic associations with plasma efavirenz concentrations and clinical correlates in a retrospective cohort of Ghanaian HIV-infected patients.
Auteurs : Fred S. Sarfo [Ghana] ; Yuan Zhang ; Deirdre Egan ; Lambert A. Tetteh ; Richard Phillips ; George Bedu-Addo ; Maame Anima Sarfo ; Saye Khoo ; Andrew Owen ; David R. ChadwickSource :
- The Journal of antimicrobial chemotherapy [ 1460-2091 ] ; 2014.
Descripteurs français
- KwdFr :
- Adolescent, Adulte, Adulte d'âge moyen, Agents antiVIH (usage thérapeutique), Aryl hydrocarbon hydroxylases (génétique), Benzoxazines (usage thérapeutique), Cytochrome P-450 CYP2A6, Cytochrome P-450 CYP2B6, Femelle, Ghana (épidémiologie), Glucuronosyltransferase (génétique), Humains, Infections à VIH (génétique), Infections à VIH (traitement médicamenteux), Infections à VIH (épidémiologie), Jeune adulte, Mâle, Polymorphisme de nucléotide simple (génétique), Sujet âgé, Études de cohortes, Études rétrospectives.
- MESH :
- génétique : Aryl hydrocarbon hydroxylases, Glucuronosyltransferase, Infections à VIH, Polymorphisme de nucléotide simple.
- traitement médicamenteux : Infections à VIH.
- usage thérapeutique : Agents antiVIH, Benzoxazines.
- épidémiologie : Ghana, Infections à VIH.
- Adolescent, Adulte, Adulte d'âge moyen, Cytochrome P-450 CYP2A6, Cytochrome P-450 CYP2B6, Femelle, Humains, Jeune adulte, Mâle, Sujet âgé, Études de cohortes, Études rétrospectives.
English descriptors
- KwdEn :
- Adolescent, Adult, Aged, Anti-HIV Agents (therapeutic use), Aryl Hydrocarbon Hydroxylases (genetics), Benzoxazines (therapeutic use), Cohort Studies, Cytochrome P-450 CYP2A6, Cytochrome P-450 CYP2B6, Female, Ghana (epidemiology), Glucuronosyltransferase (genetics), HIV Infections (drug therapy), HIV Infections (epidemiology), HIV Infections (genetics), Humans, Male, Middle Aged, Polymorphism, Single Nucleotide (genetics), Retrospective Studies, Young Adult.
- MESH :
- chemical , genetics : Aryl Hydrocarbon Hydroxylases, Glucuronosyltransferase.
- chemical , therapeutic use : Anti-HIV Agents, Benzoxazines.
- drug therapy : HIV Infections.
- epidemiology : Ghana, HIV Infections.
- genetics : HIV Infections, Polymorphism, Single Nucleotide.
- Adolescent, Adult, Aged, Cohort Studies, Cytochrome P-450 CYP2A6, Cytochrome P-450 CYP2B6, Female, Humans, Male, Middle Aged, Retrospective Studies, Young Adult.
Abstract
Efavirenz is widely used in first-line antiretroviral therapy in sub-Saharan Africa. However, exposure to efavirenz shows marked interindividual variability that is genetically mediated with potential for important pharmacodynamic consequences. The aims of this study were to assess the frequencies of CYP2B6, CYP2A6, UGT2B7 and CAR single nucleotide polymorphisms (SNPs) and their impact on plasma efavirenz concentration and clinical/immunological responses in Ghanaian patients.
DOI: 10.1093/jac/dkt372
PubMed: 24080498
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Sarfo</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicine, Komfo Anokye Teaching Hospital, Kumasi, Ghana.</nlm:affiliation><country xml:lang="fr">Ghana</country><wicri:regionArea>Department of Medicine, Komfo Anokye Teaching Hospital, Kumasi</wicri:regionArea></affiliation></author><author><name sortKey="Zhang, Yuan" sort="Zhang, Yuan" uniqKey="Zhang Y" first="Yuan" last="Zhang">Yuan Zhang</name></author><author><name sortKey="Egan, Deirdre" sort="Egan, Deirdre" uniqKey="Egan D" first="Deirdre" last="Egan">Deirdre Egan</name></author><author><name sortKey="Tetteh, Lambert A" sort="Tetteh, Lambert A" uniqKey="Tetteh L" first="Lambert A" last="Tetteh">Lambert A. Tetteh</name></author><author><name sortKey="Phillips, Richard" sort="Phillips, Richard" uniqKey="Phillips R" first="Richard" last="Phillips">Richard Phillips</name></author><author><name sortKey="Bedu Addo, George" sort="Bedu Addo, George" uniqKey="Bedu Addo G" first="George" last="Bedu-Addo">George Bedu-Addo</name></author><author><name sortKey="Sarfo, Maame Anima" sort="Sarfo, Maame Anima" uniqKey="Sarfo M" first="Maame Anima" last="Sarfo">Maame Anima Sarfo</name></author><author><name sortKey="Khoo, Saye" sort="Khoo, Saye" uniqKey="Khoo S" first="Saye" last="Khoo">Saye Khoo</name></author><author><name sortKey="Owen, Andrew" sort="Owen, Andrew" uniqKey="Owen A" first="Andrew" last="Owen">Andrew Owen</name></author><author><name sortKey="Chadwick, David R" sort="Chadwick, David R" uniqKey="Chadwick D" first="David R" last="Chadwick">David R. 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Sarfo</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicine, Komfo Anokye Teaching Hospital, Kumasi, Ghana.</nlm:affiliation><country xml:lang="fr">Ghana</country><wicri:regionArea>Department of Medicine, Komfo Anokye Teaching Hospital, Kumasi</wicri:regionArea></affiliation></author><author><name sortKey="Zhang, Yuan" sort="Zhang, Yuan" uniqKey="Zhang Y" first="Yuan" last="Zhang">Yuan Zhang</name></author><author><name sortKey="Egan, Deirdre" sort="Egan, Deirdre" uniqKey="Egan D" first="Deirdre" last="Egan">Deirdre Egan</name></author><author><name sortKey="Tetteh, Lambert A" sort="Tetteh, Lambert A" uniqKey="Tetteh L" first="Lambert A" last="Tetteh">Lambert A. Tetteh</name></author><author><name sortKey="Phillips, Richard" sort="Phillips, Richard" uniqKey="Phillips R" first="Richard" last="Phillips">Richard Phillips</name></author><author><name sortKey="Bedu Addo, George" sort="Bedu Addo, George" uniqKey="Bedu Addo G" first="George" last="Bedu-Addo">George Bedu-Addo</name></author><author><name sortKey="Sarfo, Maame Anima" sort="Sarfo, Maame Anima" uniqKey="Sarfo M" first="Maame Anima" last="Sarfo">Maame Anima Sarfo</name></author><author><name sortKey="Khoo, Saye" sort="Khoo, Saye" uniqKey="Khoo S" first="Saye" last="Khoo">Saye Khoo</name></author><author><name sortKey="Owen, Andrew" sort="Owen, Andrew" uniqKey="Owen A" first="Andrew" last="Owen">Andrew Owen</name></author><author><name sortKey="Chadwick, David R" sort="Chadwick, David R" uniqKey="Chadwick D" first="David R" last="Chadwick">David R. Chadwick</name></author></analytic><series><title level="j">The Journal of antimicrobial chemotherapy</title><idno type="eISSN">1460-2091</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adolescent</term><term>Adult</term><term>Aged</term><term>Anti-HIV Agents (therapeutic use)</term><term>Aryl Hydrocarbon Hydroxylases (genetics)</term><term>Benzoxazines (therapeutic use)</term><term>Cohort Studies</term><term>Cytochrome P-450 CYP2A6</term><term>Cytochrome P-450 CYP2B6</term><term>Female</term><term>Ghana (epidemiology)</term><term>Glucuronosyltransferase (genetics)</term><term>HIV Infections (drug therapy)</term><term>HIV Infections (epidemiology)</term><term>HIV Infections (genetics)</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Polymorphism, Single Nucleotide (genetics)</term><term>Retrospective Studies</term><term>Young Adult</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adolescent</term><term>Adulte</term><term>Adulte d'âge moyen</term><term>Agents antiVIH (usage thérapeutique)</term><term>Aryl hydrocarbon hydroxylases (génétique)</term><term>Benzoxazines (usage thérapeutique)</term><term>Cytochrome P-450 CYP2A6</term><term>Cytochrome P-450 CYP2B6</term><term>Femelle</term><term>Ghana (épidémiologie)</term><term>Glucuronosyltransferase (génétique)</term><term>Humains</term><term>Infections à VIH (génétique)</term><term>Infections à VIH (traitement médicamenteux)</term><term>Infections à VIH (épidémiologie)</term><term>Jeune adulte</term><term>Mâle</term><term>Polymorphisme de nucléotide simple (génétique)</term><term>Sujet âgé</term><term>Études de cohortes</term><term>Études rétrospectives</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Aryl Hydrocarbon Hydroxylases</term><term>Glucuronosyltransferase</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Anti-HIV Agents</term><term>Benzoxazines</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>HIV Infections</term></keywords><keywords scheme="MESH" qualifier="epidemiology" xml:lang="en"><term>Ghana</term><term>HIV Infections</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>HIV Infections</term><term>Polymorphism, Single Nucleotide</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Aryl hydrocarbon hydroxylases</term><term>Glucuronosyltransferase</term><term>Infections à VIH</term><term>Polymorphisme de nucléotide simple</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Infections à VIH</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Agents antiVIH</term><term>Benzoxazines</term></keywords><keywords scheme="MESH" qualifier="épidémiologie" xml:lang="fr"><term>Ghana</term><term>Infections à VIH</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adolescent</term><term>Adult</term><term>Aged</term><term>Cohort Studies</term><term>Cytochrome P-450 CYP2A6</term><term>Cytochrome P-450 CYP2B6</term><term>Female</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Retrospective Studies</term><term>Young Adult</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adolescent</term><term>Adulte</term><term>Adulte d'âge moyen</term><term>Cytochrome P-450 CYP2A6</term><term>Cytochrome P-450 CYP2B6</term><term>Femelle</term><term>Humains</term><term>Jeune adulte</term><term>Mâle</term><term>Sujet âgé</term><term>Études de cohortes</term><term>Études rétrospectives</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Efavirenz is widely used in first-line antiretroviral therapy in sub-Saharan Africa. However, exposure to efavirenz shows marked interindividual variability that is genetically mediated with potential for important pharmacodynamic consequences. The aims of this study were to assess the frequencies of CYP2B6, CYP2A6, UGT2B7 and CAR single nucleotide polymorphisms (SNPs) and their impact on plasma efavirenz concentration and clinical/immunological responses in Ghanaian patients.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">24080498</PMID><DateCreated><Year>2014</Year><Month>01</Month><Day>10</Day></DateCreated><DateCompleted><Year>2014</Year><Month>09</Month><Day>08</Day></DateCompleted><DateRevised><Year>2017</Year><Month>09</Month><Day>02</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1460-2091</ISSN><JournalIssue CitedMedium="Internet"><Volume>69</Volume><Issue>2</Issue><PubDate><Year>2014</Year><Month>Feb</Month></PubDate></JournalIssue><Title>The Journal of antimicrobial chemotherapy</Title><ISOAbbreviation>J. Antimicrob. Chemother.</ISOAbbreviation></Journal><ArticleTitle>Pharmacogenetic associations with plasma efavirenz concentrations and clinical correlates in a retrospective cohort of Ghanaian HIV-infected patients.</ArticleTitle><Pagination><MedlinePgn>491-9</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1093/jac/dkt372</ELocationID><Abstract><AbstractText Label="OBJECTIVES" NlmCategory="OBJECTIVE">Efavirenz is widely used in first-line antiretroviral therapy in sub-Saharan Africa. However, exposure to efavirenz shows marked interindividual variability that is genetically mediated with potential for important pharmacodynamic consequences. The aims of this study were to assess the frequencies of CYP2B6, CYP2A6, UGT2B7 and CAR single nucleotide polymorphisms (SNPs) and their impact on plasma efavirenz concentration and clinical/immunological responses in Ghanaian patients.</AbstractText><AbstractText Label="METHODS" NlmCategory="METHODS">Genomic DNA from 800 HIV-infected patients was genotyped for selected SNPs by real-time PCR-based allelic discrimination. Mid-dose plasma efavirenz concentrations were measured for 521 patients using HPLC with UV detection. Clinical outcomes in 299 patients on efavirenz were retrospectively assessed. Univariate and multivariate linear regression were performed using best subset selection. Time-to-event outcomes were analysed using a Cox proportional hazards regression model.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">The variant allele frequencies for CYP2B6 516G>T (rs3745274), CYP2B6 983T>C (rs28399499), CYP2A6 -48T>G (CYP2B6*9B; rs28399433), UGT2B7 802C>T (UGT2B7*2; rs7439366), UGT2B7 735A>G (UGT2B7*1c; rs28365062) and CAR 540C>T (rs2307424) were 48%, 4%, 3%, 23%, 15% and 7%, respectively. CYP2B6 516G>T, CYP2B6 983T>C and CYP2A6 -48T>G were associated with significantly elevated efavirenz concentrations. A trend towards association between plasma efavirenz concentration and CAR 540C>T was observed. CYP2B6 516G homozygosity was associated with immunological failure [adjusted hazards ratio compared with T homozygosity, 1.70 (1.04-2.76); P = 0.03].</AbstractText><AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">CYP2B6 and CYP2A6 SNPs were associated with higher plasma efavirenz concentrations due to reduction in major and minor phase I routes of elimination, respectively. Further prospective studies are needed to validate the pharmacodynamic correlates of these polymorphisms in this population.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Sarfo</LastName><ForeName>Fred S</ForeName><Initials>FS</Initials><AffiliationInfo><Affiliation>Department of Medicine, Komfo Anokye Teaching Hospital, Kumasi, Ghana.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Yuan</ForeName><Initials>Y</Initials></Author><Author ValidYN="Y"><LastName>Egan</LastName><ForeName>Deirdre</ForeName><Initials>D</Initials></Author><Author ValidYN="Y"><LastName>Tetteh</LastName><ForeName>Lambert A</ForeName><Initials>LA</Initials></Author><Author ValidYN="Y"><LastName>Phillips</LastName><ForeName>Richard</ForeName><Initials>R</Initials></Author><Author ValidYN="Y"><LastName>Bedu-Addo</LastName><ForeName>George</ForeName><Initials>G</Initials></Author><Author ValidYN="Y"><LastName>Sarfo</LastName><ForeName>Maame Anima</ForeName><Initials>MA</Initials></Author><Author ValidYN="Y"><LastName>Khoo</LastName><ForeName>Saye</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Owen</LastName><ForeName>Andrew</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Chadwick</LastName><ForeName>David R</ForeName><Initials>DR</Initials></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>MRC_G0800247</GrantID><Agency>Medical Research Council</Agency><Country>United Kingdom</Country></Grant><Grant><GrantID>MRC_G0901364</GrantID><Agency>Medical Research Council</Agency><Country>United Kingdom</Country></Grant><Grant><GrantID>MRC_MR/J01477X/1</GrantID><Agency>Medical Research Council</Agency><Country>United Kingdom</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2013</Year><Month>09</Month><Day>29</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>J Antimicrob Chemother</MedlineTA><NlmUniqueID>7513617</NlmUniqueID><ISSNLinking>0305-7453</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D019380">Anti-HIV Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D048588">Benzoxazines</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 1.14.14.1</RegistryNumber><NameOfSubstance UI="D001189">Aryl Hydrocarbon Hydroxylases</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 1.14.14.1</RegistryNumber><NameOfSubstance UI="C585710">CYP2A6 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 1.14.14.1</RegistryNumber><NameOfSubstance UI="C585599">CYP2B6 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 1.14.14.1</RegistryNumber><NameOfSubstance UI="D065637">Cytochrome P-450 CYP2A6</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 1.14.14.1</RegistryNumber><NameOfSubstance UI="D065702">Cytochrome P-450 CYP2B6</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.4.1.-</RegistryNumber><NameOfSubstance UI="C491474">UGT2B7 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.4.1.17</RegistryNumber><NameOfSubstance UI="D014453">Glucuronosyltransferase</NameOfSubstance></Chemical><Chemical><RegistryNumber>JE6H2O27P8</RegistryNumber><NameOfSubstance UI="C098320">efavirenz</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000293" MajorTopicYN="N">Adolescent</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000368" MajorTopicYN="N">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D019380" MajorTopicYN="N">Anti-HIV Agents</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001189" MajorTopicYN="N">Aryl Hydrocarbon Hydroxylases</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D048588" MajorTopicYN="N">Benzoxazines</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015331" MajorTopicYN="N">Cohort Studies</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D065637" MajorTopicYN="N">Cytochrome P-450 CYP2A6</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D065702" MajorTopicYN="N">Cytochrome P-450 CYP2B6</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005869" MajorTopicYN="N">Ghana</DescriptorName><QualifierName UI="Q000453" MajorTopicYN="N">epidemiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014453" MajorTopicYN="N">Glucuronosyltransferase</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015658" MajorTopicYN="N">HIV Infections</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName><QualifierName UI="Q000453" MajorTopicYN="N">epidemiology</QualifierName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D020641" MajorTopicYN="N">Polymorphism, Single Nucleotide</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D012189" MajorTopicYN="N">Retrospective Studies</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D055815" MajorTopicYN="N">Young Adult</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Africa</Keyword><Keyword MajorTopicYN="N">non-nucleoside reverse transcriptase inhibitors</Keyword><Keyword MajorTopicYN="N">pharmacodynamics</Keyword><Keyword MajorTopicYN="N">pharmacokinetics</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2013</Year><Month>10</Month><Day>2</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate 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