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David W Haas - One of the best experts on this subject based on the ideXlab platform.
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brain Neurotransmitter Transporter receptor genomics and efavirenz central nervous system adverse events
Pharmacogenetics and Genomics, 2018Co-Authors: David W Haas, Yuki Bradford, Anurag Verma, Shefali S Verma, Joseph J Eron, Roy M Gulick, Sharon A Riddler, Eric S Daar, Gene D MorseAbstract:OBJECTIVE: We characterized associations between central nervous system (CNS) adverse events and brain Neurotransmitter Transporter/receptor genomics among participants randomized to efavirenz-containing regimens in AIDS Clinical Trials Group studies in the USA. PARTICIPANTS AND METHODS: Four clinical trials randomly assigned treatment-naive participants to efavirenz-containing regimens. Genome-wide genotype and PrediXcan were used to infer gene expression levels in tissues including 10 brain regions. Multivariable regression models stratified by race/ethnicity were adjusted for CYP2B6/CYP2A6 genotypes that predict plasma efavirenz exposure, age, and sex. Combined analyses also adjusted for genetic ancestry. RESULTS: Analyses included 167 cases with grade 2 or greater efavirenz-consistent CNS adverse events within 48 weeks of study entry, and 653 efavirenz-tolerant controls. CYP2B6/CYP2A6 genotype level was independently associated with CNS adverse events (odds ratio: 1.07; P=0.044). Predicted expression of six genes postulated to mediate efavirenz CNS side effects (SLC6A2, SLC6A3, PGR, HTR2A, HTR2B, HTR6) were not associated with CNS adverse events after correcting for multiple testing, the lowest P value being for PGR in hippocampus (P=0.012), nor were polymorphisms in these genes or AR and HTR2C, the lowest P value being for rs12393326 in HTR2C (P=6.7×10(-4)). As a positive control, baseline plasma bilirubin concentration was associated with predicted liver UGT1A1 expression level (P=1.9×10(-27)). CONCLUSION: Efavirenz-related CNS adverse events were not associated with predicted Neurotransmitter Transporter/receptor gene expression levels in brain or with polymorphisms in these genes. Variable susceptibility to efavirenz-related CNS adverse events may not be explained by brain Neurotransmitter Transporter/receptor genomics.
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Brain Neurotransmitter Transporter/receptor genomics and efavirenz central nervous system adverse events.
Pharmacogenetics and genomics, 2018Co-Authors: David W Haas, Yuki Bradford, Anurag Verma, Shefali S Verma, Joseph J Eron, Roy M Gulick, Sharon A Riddler, Eric S Daar, Paul E. Sax, Gene D MorseAbstract:OBJECTIVE We characterized associations between central nervous system (CNS) adverse events and brain Neurotransmitter Transporter/receptor genomics among participants randomized to efavirenz-containing regimens in AIDS Clinical Trials Group studies in the USA. PARTICIPANTS AND METHODS Four clinical trials randomly assigned treatment-naive participants to efavirenz-containing regimens. Genome-wide genotype and PrediXcan were used to infer gene expression levels in tissues including 10 brain regions. Multivariable regression models stratified by race/ethnicity were adjusted for CYP2B6/CYP2A6 genotypes that predict plasma efavirenz exposure, age, and sex. Combined analyses also adjusted for genetic ancestry. RESULTS Analyses included 167 cases with grade 2 or greater efavirenz-consistent CNS adverse events within 48 weeks of study entry, and 653 efavirenz-tolerant controls. CYP2B6/CYP2A6 genotype level was independently associated with CNS adverse events (odds ratio: 1.07; P=0.044). Predicted expression of six genes postulated to mediate efavirenz CNS side effects (SLC6A2, SLC6A3, PGR, HTR2A, HTR2B, HTR6) were not associated with CNS adverse events after correcting for multiple testing, the lowest P value being for PGR in hippocampus (P=0.012), nor were polymorphisms in these genes or AR and HTR2C, the lowest P value being for rs12393326 in HTR2C (P=6.7×10(-4)). As a positive control, baseline plasma bilirubin concentration was associated with predicted liver UGT1A1 expression level (P=1.9×10(-27)). CONCLUSION Efavirenz-related CNS adverse events were not associated with predicted Neurotransmitter Transporter/receptor gene expression levels in brain or with polymorphisms in these genes. Variable susceptibility to efavirenz-related CNS adverse events may not be explained by brain Neurotransmitter Transporter/receptor genomics.
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brain Neurotransmitter Transporter receptor genomics and efavirenz central nervous system adverse events
Pharmacogenetics and Genomics, 2018Co-Authors: David W Haas, Yuki Bradford, Anurag Verma, Shefali S Verma, Joseph J Eron, Roy M Gulick, Sharon A Riddler, Paul E. Sax, Eric S DaarAbstract:OBJECTIVE We characterized associations between central nervous system (CNS) adverse events and brain Neurotransmitter Transporter/receptor genomics among participants randomized to efavirenz-containing regimens in AIDS Clinical Trials Group studies in the USA. PARTICIPANTS AND METHODS Four clinical trials randomly assigned treatment-naive participants to efavirenz-containing regimens. Genome-wide genotype and PrediXcan were used to infer gene expression levels in tissues including 10 brain regions. Multivariable regression models stratified by race/ethnicity were adjusted for CYP2B6/CYP2A6 genotypes that predict plasma efavirenz exposure, age, and sex. Combined analyses also adjusted for genetic ancestry. RESULTS Analyses included 167 cases with grade 2 or greater efavirenz-consistent CNS adverse events within 48 weeks of study entry, and 653 efavirenz-tolerant controls. CYP2B6/CYP2A6 genotype level was independently associated with CNS adverse events (odds ratio: 1.07; P=0.044). Predicted expression of six genes postulated to mediate efavirenz CNS side effects (SLC6A2, SLC6A3, PGR, HTR2A, HTR2B, HTR6) were not associated with CNS adverse events after correcting for multiple testing, the lowest P value being for PGR in hippocampus (P=0.012), nor were polymorphisms in these genes or AR and HTR2C, the lowest P value being for rs12393326 in HTR2C (P=6.7×10(-4)). As a positive control, baseline plasma bilirubin concentration was associated with predicted liver UGT1A1 expression level (P=1.9×10(-27)). CONCLUSION Efavirenz-related CNS adverse events were not associated with predicted Neurotransmitter Transporter/receptor gene expression levels in brain or with polymorphisms in these genes. Variable susceptibility to efavirenz-related CNS adverse events may not be explained by brain Neurotransmitter Transporter/receptor genomics.
Gary Rudnick - One of the best experts on this subject based on the ideXlab platform.
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slc6 Neurotransmitter Transporter family version 2019 4 in the iuphar bps guide to pharmacology database
IUPHAR BPS Guide to Pharmacology CITE, 2019Co-Authors: Stefan Bröer, Gary RudnickAbstract:Members of the solute carrier family 6 (SLC6) of sodium- and (sometimes chloride-) dependent Neurotransmitter Transporters [29, 22, 70] are primarily plasma membrane located and may be divided into four subfamilies that transport monoamines, GABA, glycine and neutral amino acids, plus the related bacterial NSS Transporters [99]. The members of this superfamily share a structural motif of 10 TM segments that has been observed in crystal structures of the NSS bacterial homolog LeuTAa, a Na+-dependent amino acid Transporter from Aquiflex aeolicus [126] and in several other Transporter families structurally related to LeuT [45].
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SLC6 Neurotransmitter Transporter family (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
IUPHAR BPS Guide to Pharmacology CITE, 2019Co-Authors: Stefan Bröer, Gary RudnickAbstract:Members of the solute carrier family 6 (SLC6) of sodium- and (sometimes chloride-) dependent Neurotransmitter Transporters [29, 22, 70] are primarily plasma membrane located and may be divided into four subfamilies that transport monoamines, GABA, glycine and neutral amino acids, plus the related bacterial NSS Transporters [99]. The members of this superfamily share a structural motif of 10 TM segments that has been observed in crystal structures of the NSS bacterial homolog LeuTAa, a Na+-dependent amino acid Transporter from Aquiflex aeolicus [126] and in several other Transporter families structurally related to LeuT [45].
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structural elements required for coupling ion and substrate transport in the Neurotransmitter Transporter homolog leut
Proceedings of the National Academy of Sciences of the United States of America, 2018Co-Authors: Sotiria Tavoulari, Lucy R. Forrest, Yuan-wei Zhang, Steffen Sinning, Antoniya A Aleksandrova, Gary RudnickAbstract:The coupled transport of ions and substrates allows Transporters to accumulate substrates using the energy of transmembrane ion gradients and electrical potentials. During transport, conformational changes that switch accessibility of substrate and ion binding sites from one side of the membrane to the other must be controlled so as to prevent uncoupled movement of ions or substrates. In the Neurotransmitter:sodium symporter (NSS) family, Na+ stabilizes the Transporter in an outward-open state, thus decreasing the likelihood of uncoupled Na+ transport. Substrate binding, in a step essential for coupled transport, must overcome the effect of Na+, allowing intracellular substrate and Na+ release from an inward-open state. However, the specific elements of the protein that mediate this conformational response to substrate binding are unknown. Previously, we showed that in the prokaryotic NSS Transporter LeuT, the effect of Na+ on conformation requires the Na2 site, where it influences conformation by fostering interaction between two domains of the protein. Here, we used cysteine accessibility to measure conformational changes of LeuT in Escherichia coli membranes. We identified a conserved tyrosine residue in the substrate binding site required for substrate to convert LeuT to inward-open states by establishing an interaction between the two Transporter domains. We further identify additional required interactions between the two Transporter domains in the extracellular pathway. Together with our previous work on the conformational effect of Na+, these results identify mechanistic components underlying ion–substrate coupling in NSS Transporters.
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structural elements required for coupling ion and substrate transport in the Neurotransmitter Transporter homolog leut
bioRxiv, 2018Co-Authors: Yuan-wei Zhang, Sotiria Tavoulari, Lucy R. Forrest, Steffen Sinning, Antoniya A Aleksandrova, Gary RudnickAbstract:The coupled transport of ions and substrates allows Transporters to accumulate substrates using the energy in transmembrane ion gradients and electrical potentials. During transport, conformational changes that switch accessibility of substrate and ion binding sites from one side of the membrane to the other must be controlled so as to prevent uncoupled movement of ions or substrates. In the Neurotransmitter:Sodium Symporter (NSS) family, Na+ stabilizes the Transporter in an outward-open state, thus decreasing the likelihood of uncoupled Na+ transport. In a step essential for coupled transport, substrate binding must overcome the effect of Na+, allowing intracellular substrate and Na+ release from an inward-open state. However, it is unclear which specific elements of the protein mediate this conformational response to substrate binding. Previously, we showed that in the prokaryotic NSS Transporter LeuT, the effect of Na+ on conformation occurs at the Na2 site, where it influences conformation by fostering interaction between two domains of the protein (JBC 291: 1456, 2016). Here, we identify a conserved tyrosine residue in the substrate binding site required for substrate to enable conversion to inward-open states by establishing an interaction between the two Transporter domains. We further identify additional interactions between the two Transporter domains in the extracellular pathway that are required. Together with our previous work on the conformational effect of Na+, these results identify mechanistic components underlying ion-substrate coupling in NSS Transporters.
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two na sites control conformational change in a Neurotransmitter Transporter homolog
Journal of Biological Chemistry, 2016Co-Authors: Sotiria Tavoulari, Lucy R. Forrest, Eleonora Margheritis, Anu Nagarajan, David C. Dewitt, Yuan-wei Zhang, Edwin Rosado, Silvia Ravera, Elizabeth Rhoades, Gary RudnickAbstract:In LeuT, a prokaryotic homolog of Neurotransmitter Transporters, Na(+) stabilizes outward-open conformational states. We examined how each of the two LeuT Na(+) binding sites contributes to Na(+)-dependent closure of the cytoplasmic pathway using biochemical and biophysical assays of conformation. Mutating either of two residues that contribute to the Na2 site completely prevented cytoplasmic closure in response to Na(+), suggesting that Na2 is essential for this conformational change, whereas Na1 mutants retained Na(+) responsiveness. However, mutation of Na1 residues also influenced the Na(+)-dependent conformational change in ways that varied depending on the position mutated. Computational analyses suggest those mutants influence the ability of Na1 binding to hydrate the substrate pathway and perturb an interaction network leading to the extracellular gate. Overall, the results demonstrate that occupation of Na2 stabilizes outward-facing conformations presumably through a direct interaction between Na(+) and transmembrane helices 1 and 8, whereas Na(+) binding at Na1 influences conformational change through a network of intermediary interactions. The results also provide evidence that N-terminal release and helix motions represent distinct steps in cytoplasmic pathway opening.
David E. Krantz - One of the best experts on this subject based on the ideXlab platform.
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vesicular Neurotransmitter Transporter trafficking in vivo moving from cells to flies
Fly, 2010Co-Authors: Anna Grygoruk, Hao Fei, Richard W. Daniels, Bradley R. Miller, Audrey Chen, Aaron Diantonio, David E. KrantzAbstract:During exocytosis, classical and amino acid Neurotransmitters are released from the lumen of synaptic vesicles to allow signaling at the synapse. The storage of Neurotransmitters in synaptic vesicles and other types of secretory vesicles requires the activity of specific vesicular Transporters. Glutamate and monoamines such as dopamine are packaged by VGLUTs and VMATs respectively. Changes in the localization of either protein have the potential to up- or down regulate Neurotransmitter release, and some of the mechanisms for sorting these proteins to secretory vesicles have been investigated in cultured cells in vitro. We have used Drosophila molecular genetic techniques to study vesicular Transporter trafficking in an intact organism and have identified a motif required for localizing Drosophila VMAT (DVMAT) to synaptic vesicles in vivo. In contrast to DVMAT, large deletions of Drosophila VGLUT (DVGLUT) show relatively modest deficits in localizing to synaptic vesicles, suggesting that DVMAT and DVGLUT m...
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Vesicular Neurotransmitter Transporter trafficking in vivo
Fly, 2010Co-Authors: Anna Grygoruk, Hao Fei, Richard W. Daniels, Bradley R. Miller, Audrey Chen, Aaron Diantonio, David E. KrantzAbstract:VMAT, VGLUT, vesicular Neurotransmitter Transporter, membrane trafficking, tyrosine motif, synaptic vesicle (SV), large dense core vesicle (LDCV)Submitted: 06/28/10Revised: 08/09/10Accepted: 08/10/10Previously published online: www.landesbioscience.com/journals/fly/article/13305DOI: 10.4161/fly.4.4.13305
Gene D Morse - One of the best experts on this subject based on the ideXlab platform.
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brain Neurotransmitter Transporter receptor genomics and efavirenz central nervous system adverse events
Pharmacogenetics and Genomics, 2018Co-Authors: David W Haas, Yuki Bradford, Anurag Verma, Shefali S Verma, Joseph J Eron, Roy M Gulick, Sharon A Riddler, Eric S Daar, Gene D MorseAbstract:OBJECTIVE: We characterized associations between central nervous system (CNS) adverse events and brain Neurotransmitter Transporter/receptor genomics among participants randomized to efavirenz-containing regimens in AIDS Clinical Trials Group studies in the USA. PARTICIPANTS AND METHODS: Four clinical trials randomly assigned treatment-naive participants to efavirenz-containing regimens. Genome-wide genotype and PrediXcan were used to infer gene expression levels in tissues including 10 brain regions. Multivariable regression models stratified by race/ethnicity were adjusted for CYP2B6/CYP2A6 genotypes that predict plasma efavirenz exposure, age, and sex. Combined analyses also adjusted for genetic ancestry. RESULTS: Analyses included 167 cases with grade 2 or greater efavirenz-consistent CNS adverse events within 48 weeks of study entry, and 653 efavirenz-tolerant controls. CYP2B6/CYP2A6 genotype level was independently associated with CNS adverse events (odds ratio: 1.07; P=0.044). Predicted expression of six genes postulated to mediate efavirenz CNS side effects (SLC6A2, SLC6A3, PGR, HTR2A, HTR2B, HTR6) were not associated with CNS adverse events after correcting for multiple testing, the lowest P value being for PGR in hippocampus (P=0.012), nor were polymorphisms in these genes or AR and HTR2C, the lowest P value being for rs12393326 in HTR2C (P=6.7×10(-4)). As a positive control, baseline plasma bilirubin concentration was associated with predicted liver UGT1A1 expression level (P=1.9×10(-27)). CONCLUSION: Efavirenz-related CNS adverse events were not associated with predicted Neurotransmitter Transporter/receptor gene expression levels in brain or with polymorphisms in these genes. Variable susceptibility to efavirenz-related CNS adverse events may not be explained by brain Neurotransmitter Transporter/receptor genomics.
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Brain Neurotransmitter Transporter/receptor genomics and efavirenz central nervous system adverse events.
Pharmacogenetics and genomics, 2018Co-Authors: David W Haas, Yuki Bradford, Anurag Verma, Shefali S Verma, Joseph J Eron, Roy M Gulick, Sharon A Riddler, Eric S Daar, Paul E. Sax, Gene D MorseAbstract:OBJECTIVE We characterized associations between central nervous system (CNS) adverse events and brain Neurotransmitter Transporter/receptor genomics among participants randomized to efavirenz-containing regimens in AIDS Clinical Trials Group studies in the USA. PARTICIPANTS AND METHODS Four clinical trials randomly assigned treatment-naive participants to efavirenz-containing regimens. Genome-wide genotype and PrediXcan were used to infer gene expression levels in tissues including 10 brain regions. Multivariable regression models stratified by race/ethnicity were adjusted for CYP2B6/CYP2A6 genotypes that predict plasma efavirenz exposure, age, and sex. Combined analyses also adjusted for genetic ancestry. RESULTS Analyses included 167 cases with grade 2 or greater efavirenz-consistent CNS adverse events within 48 weeks of study entry, and 653 efavirenz-tolerant controls. CYP2B6/CYP2A6 genotype level was independently associated with CNS adverse events (odds ratio: 1.07; P=0.044). Predicted expression of six genes postulated to mediate efavirenz CNS side effects (SLC6A2, SLC6A3, PGR, HTR2A, HTR2B, HTR6) were not associated with CNS adverse events after correcting for multiple testing, the lowest P value being for PGR in hippocampus (P=0.012), nor were polymorphisms in these genes or AR and HTR2C, the lowest P value being for rs12393326 in HTR2C (P=6.7×10(-4)). As a positive control, baseline plasma bilirubin concentration was associated with predicted liver UGT1A1 expression level (P=1.9×10(-27)). CONCLUSION Efavirenz-related CNS adverse events were not associated with predicted Neurotransmitter Transporter/receptor gene expression levels in brain or with polymorphisms in these genes. Variable susceptibility to efavirenz-related CNS adverse events may not be explained by brain Neurotransmitter Transporter/receptor genomics.
Eric S Daar - One of the best experts on this subject based on the ideXlab platform.
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brain Neurotransmitter Transporter receptor genomics and efavirenz central nervous system adverse events
Pharmacogenetics and Genomics, 2018Co-Authors: David W Haas, Yuki Bradford, Anurag Verma, Shefali S Verma, Joseph J Eron, Roy M Gulick, Sharon A Riddler, Eric S Daar, Gene D MorseAbstract:OBJECTIVE: We characterized associations between central nervous system (CNS) adverse events and brain Neurotransmitter Transporter/receptor genomics among participants randomized to efavirenz-containing regimens in AIDS Clinical Trials Group studies in the USA. PARTICIPANTS AND METHODS: Four clinical trials randomly assigned treatment-naive participants to efavirenz-containing regimens. Genome-wide genotype and PrediXcan were used to infer gene expression levels in tissues including 10 brain regions. Multivariable regression models stratified by race/ethnicity were adjusted for CYP2B6/CYP2A6 genotypes that predict plasma efavirenz exposure, age, and sex. Combined analyses also adjusted for genetic ancestry. RESULTS: Analyses included 167 cases with grade 2 or greater efavirenz-consistent CNS adverse events within 48 weeks of study entry, and 653 efavirenz-tolerant controls. CYP2B6/CYP2A6 genotype level was independently associated with CNS adverse events (odds ratio: 1.07; P=0.044). Predicted expression of six genes postulated to mediate efavirenz CNS side effects (SLC6A2, SLC6A3, PGR, HTR2A, HTR2B, HTR6) were not associated with CNS adverse events after correcting for multiple testing, the lowest P value being for PGR in hippocampus (P=0.012), nor were polymorphisms in these genes or AR and HTR2C, the lowest P value being for rs12393326 in HTR2C (P=6.7×10(-4)). As a positive control, baseline plasma bilirubin concentration was associated with predicted liver UGT1A1 expression level (P=1.9×10(-27)). CONCLUSION: Efavirenz-related CNS adverse events were not associated with predicted Neurotransmitter Transporter/receptor gene expression levels in brain or with polymorphisms in these genes. Variable susceptibility to efavirenz-related CNS adverse events may not be explained by brain Neurotransmitter Transporter/receptor genomics.
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Brain Neurotransmitter Transporter/receptor genomics and efavirenz central nervous system adverse events.
Pharmacogenetics and genomics, 2018Co-Authors: David W Haas, Yuki Bradford, Anurag Verma, Shefali S Verma, Joseph J Eron, Roy M Gulick, Sharon A Riddler, Eric S Daar, Paul E. Sax, Gene D MorseAbstract:OBJECTIVE We characterized associations between central nervous system (CNS) adverse events and brain Neurotransmitter Transporter/receptor genomics among participants randomized to efavirenz-containing regimens in AIDS Clinical Trials Group studies in the USA. PARTICIPANTS AND METHODS Four clinical trials randomly assigned treatment-naive participants to efavirenz-containing regimens. Genome-wide genotype and PrediXcan were used to infer gene expression levels in tissues including 10 brain regions. Multivariable regression models stratified by race/ethnicity were adjusted for CYP2B6/CYP2A6 genotypes that predict plasma efavirenz exposure, age, and sex. Combined analyses also adjusted for genetic ancestry. RESULTS Analyses included 167 cases with grade 2 or greater efavirenz-consistent CNS adverse events within 48 weeks of study entry, and 653 efavirenz-tolerant controls. CYP2B6/CYP2A6 genotype level was independently associated with CNS adverse events (odds ratio: 1.07; P=0.044). Predicted expression of six genes postulated to mediate efavirenz CNS side effects (SLC6A2, SLC6A3, PGR, HTR2A, HTR2B, HTR6) were not associated with CNS adverse events after correcting for multiple testing, the lowest P value being for PGR in hippocampus (P=0.012), nor were polymorphisms in these genes or AR and HTR2C, the lowest P value being for rs12393326 in HTR2C (P=6.7×10(-4)). As a positive control, baseline plasma bilirubin concentration was associated with predicted liver UGT1A1 expression level (P=1.9×10(-27)). CONCLUSION Efavirenz-related CNS adverse events were not associated with predicted Neurotransmitter Transporter/receptor gene expression levels in brain or with polymorphisms in these genes. Variable susceptibility to efavirenz-related CNS adverse events may not be explained by brain Neurotransmitter Transporter/receptor genomics.
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brain Neurotransmitter Transporter receptor genomics and efavirenz central nervous system adverse events
Pharmacogenetics and Genomics, 2018Co-Authors: David W Haas, Yuki Bradford, Anurag Verma, Shefali S Verma, Joseph J Eron, Roy M Gulick, Sharon A Riddler, Paul E. Sax, Eric S DaarAbstract:OBJECTIVE We characterized associations between central nervous system (CNS) adverse events and brain Neurotransmitter Transporter/receptor genomics among participants randomized to efavirenz-containing regimens in AIDS Clinical Trials Group studies in the USA. PARTICIPANTS AND METHODS Four clinical trials randomly assigned treatment-naive participants to efavirenz-containing regimens. Genome-wide genotype and PrediXcan were used to infer gene expression levels in tissues including 10 brain regions. Multivariable regression models stratified by race/ethnicity were adjusted for CYP2B6/CYP2A6 genotypes that predict plasma efavirenz exposure, age, and sex. Combined analyses also adjusted for genetic ancestry. RESULTS Analyses included 167 cases with grade 2 or greater efavirenz-consistent CNS adverse events within 48 weeks of study entry, and 653 efavirenz-tolerant controls. CYP2B6/CYP2A6 genotype level was independently associated with CNS adverse events (odds ratio: 1.07; P=0.044). Predicted expression of six genes postulated to mediate efavirenz CNS side effects (SLC6A2, SLC6A3, PGR, HTR2A, HTR2B, HTR6) were not associated with CNS adverse events after correcting for multiple testing, the lowest P value being for PGR in hippocampus (P=0.012), nor were polymorphisms in these genes or AR and HTR2C, the lowest P value being for rs12393326 in HTR2C (P=6.7×10(-4)). As a positive control, baseline plasma bilirubin concentration was associated with predicted liver UGT1A1 expression level (P=1.9×10(-27)). CONCLUSION Efavirenz-related CNS adverse events were not associated with predicted Neurotransmitter Transporter/receptor gene expression levels in brain or with polymorphisms in these genes. Variable susceptibility to efavirenz-related CNS adverse events may not be explained by brain Neurotransmitter Transporter/receptor genomics.