PXR and CAR single nucleotide polymorphisms influence plasma efavirenz levels in South African HIV/AIDS patients

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dc.contributor.authorSwart, Marelizeen_ZA
dc.contributor.authorWhitehorn, Heatheren_ZA
dc.contributor.authorRen, Yuanen_ZA
dc.contributor.authorSmith, Peteren_ZA
dc.contributor.authorRamesar, Rajkumaren_ZA
dc.contributor.authorDandara, Colleten_ZA
dc.date.accessioned2015-11-23T11:45:02Z
dc.date.available2015-11-23T11:45:02Z
dc.date.issued2012en_ZA
dc.description.abstractBACKGROUND: This study investigated variation in NR1I2 and NR1I3 and its effect on plasma efavirenz levels in HIV/AIDS patients. Variability in plasma drug levels has largely led research on identifying causative variants in drug metabolising enzyme (DME) genes, with little focus on the nuclear receptor genes NR1I2 and NR1I3, coding for PXR and CAR, respectively, that are involved in regulating DMEs. METHODS: 464 Bantu-speaking South Africans comprising of HIV/AIDS patients on efavirenz-based treatment (n=301) and 163 healthy subjects were genotyped for 6 SNPs in NR1I2 and NR1I3. 32 of the 301 patients had their DNA binding domains (DBDs) in NR1I2 and NR1I3 sequenced. RESULTS: Significantly decreased efavirenz plasma concentrations were observed in patients carrying the NR1I3 rs3003596C/C and T/C genotypes (P=0.015 and P=0.010, respectively). Sequencing resulted in the discovery of a further 13 SNPs, 3 of which are novel variants in the DBD of NR1I2. There were significant differences in the distribution of NR1I2 and NR1I3 SNPs between South Africans when compared to Caucasian, Asian and Yoruba population groups. CONCLUSION: For the realisation of personalised medicine, PXR and CAR genetic variation should be taken into consideration because of their involvement in the regulation of DMEs.en_ZA
dc.identifier.apacitationSwart, M., Whitehorn, H., Ren, Y., Smith, P., Ramesar, R., & Dandara, C. (2012). PXR and CAR single nucleotide polymorphisms influence plasma efavirenz levels in South African HIV/AIDS patients. <i>BMC Medical Genetics</i>, http://hdl.handle.net/11427/15246en_ZA
dc.identifier.chicagocitationSwart, Marelize, Heather Whitehorn, Yuan Ren, Peter Smith, Rajkumar Ramesar, and Collet Dandara "PXR and CAR single nucleotide polymorphisms influence plasma efavirenz levels in South African HIV/AIDS patients." <i>BMC Medical Genetics</i> (2012) http://hdl.handle.net/11427/15246en_ZA
dc.identifier.citationSwart, M., Whitehorn, H., Ren, Y., Smith, P., Ramesar, R. S., & Dandara, C. (2012). PXR and CAR single nucleotide polymorphisms influence plasma efavirenz levels in South African HIV/AIDS patients. BMC medical genetics, 13(1), 112.en_ZA
dc.identifier.ris TY - Journal Article AU - Swart, Marelize AU - Whitehorn, Heather AU - Ren, Yuan AU - Smith, Peter AU - Ramesar, Rajkumar AU - Dandara, Collet AB - BACKGROUND: This study investigated variation in NR1I2 and NR1I3 and its effect on plasma efavirenz levels in HIV/AIDS patients. Variability in plasma drug levels has largely led research on identifying causative variants in drug metabolising enzyme (DME) genes, with little focus on the nuclear receptor genes NR1I2 and NR1I3, coding for PXR and CAR, respectively, that are involved in regulating DMEs. METHODS: 464 Bantu-speaking South Africans comprising of HIV/AIDS patients on efavirenz-based treatment (n=301) and 163 healthy subjects were genotyped for 6 SNPs in NR1I2 and NR1I3. 32 of the 301 patients had their DNA binding domains (DBDs) in NR1I2 and NR1I3 sequenced. RESULTS: Significantly decreased efavirenz plasma concentrations were observed in patients carrying the NR1I3 rs3003596C/C and T/C genotypes (P=0.015 and P=0.010, respectively). Sequencing resulted in the discovery of a further 13 SNPs, 3 of which are novel variants in the DBD of NR1I2. There were significant differences in the distribution of NR1I2 and NR1I3 SNPs between South Africans when compared to Caucasian, Asian and Yoruba population groups. CONCLUSION: For the realisation of personalised medicine, PXR and CAR genetic variation should be taken into consideration because of their involvement in the regulation of DMEs. DA - 2012 DB - OpenUCT DO - 10.1186/1471-2350-13-112 DP - University of Cape Town J1 - BMC Medical Genetics LK - https://open.uct.ac.za PB - University of Cape Town PY - 2012 T1 - PXR and CAR single nucleotide polymorphisms influence plasma efavirenz levels in South African HIV/AIDS patients TI - PXR and CAR single nucleotide polymorphisms influence plasma efavirenz levels in South African HIV/AIDS patients UR - http://hdl.handle.net/11427/15246 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/15246
dc.identifier.urihttp://dx.doi.org/10.1186/1471-2350-13-112
dc.identifier.vancouvercitationSwart M, Whitehorn H, Ren Y, Smith P, Ramesar R, Dandara C. PXR and CAR single nucleotide polymorphisms influence plasma efavirenz levels in South African HIV/AIDS patients. BMC Medical Genetics. 2012; http://hdl.handle.net/11427/15246.en_ZA
dc.language.isoengen_ZA
dc.publisherBioMed Central Ltden_ZA
dc.publisher.departmentDivision of Human Geneticsen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution Licenseen_ZA
dc.rights.holder2012 Swart et al.; licensee BioMed Central Ltd.en_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/2.0en_ZA
dc.sourceBMC Medical Geneticsen_ZA
dc.source.urihttp://www.biomedcentral.com/bmcmedgenet/en_ZA
dc.subject.otherCARen_ZA
dc.subject.otherEfavirenzen_ZA
dc.subject.otherHIV/AIDSen_ZA
dc.subject.otherPXRen_ZA
dc.subject.otherPharmacogeneticsen_ZA
dc.subject.otherSouth Africaen_ZA
dc.titlePXR and CAR single nucleotide polymorphisms influence plasma efavirenz levels in South African HIV/AIDS patientsen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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