ArticleAIDS (London, England)2012
Underlying genetic structure impacts the association between CYP2B6 polymorphisms and response to efavirenz and nevirapine.
Article in AIDS (London, England), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Meta-analysis of the associations of CYP2B6-516G>T polymorphisms with efavirenz-induced central nervous system side effects and virological outcome in HIV-infected adults.The pharmacogenomics journal · 2020Pooled it
- A genomic variant of ALPK2 is associated with increased liver fibrosis risk in HIV/HCV coinfected women.PloS one · 2021Article
- Association ofPharmacogenomics and personalized medicine · 2021Article
- Polypharmacy in HIV: recent insights and future directions.Current opinion in HIV and AIDS · 2020Review
- Genome-wide admixture and association study of subclinical atherosclerosis in the Women's Interagency HIV Study (WIHS).PloS one · 2017Article
- Associations of Genetically Determined Continental Ancestry With CD4+ Count and Plasma HIV-1 RNA Beyond Self-Reported Race and Ethnicity.Journal of acquired immune deficiency syndromes (1999) · 2016Article
- Diversity in Clinical and Biomedical Research: A Promise Yet to Be Fulfilled.PLoS medicine · 2015Article
- Pharmacogenetics as a tool to tailor antiretroviral therapy: A review.World journal of virology · 2015Review
- PharmGKB summary: Efavirenz pathway, pharmacokinetics.Pharmacogenetics and genomics · 2015Review
- APOL1 Genotype and Glomerular and Tubular Kidney Injury in Women With HIV.American journal of kidney diseases : the official journal of the National Kidney Foundation · 2015Observational
- Low-frequency drug-resistant HIV-1 and risk of virological failure to first-line NNRTI-based ART: a multicohort European case-control study using centralized ultrasensitive 454 pyrosequencing.The Journal of antimicrobial chemotherapy · 2015Article
- Association of Toll-like receptor polymorphisms with HIV status in North Americans.Genes and immunity · 2014Article
- CYP2B6 c.983T>C polymorphism is associated with nevirapine hypersensitivity in Malawian and Ugandan HIV populations.The Journal of antimicrobial chemotherapy · 2014Article
- Antiretroviral therapy modifies the genetic effect of known type 2 diabetes-associated risk variants in HIV-infected women.AIDS (London, England) · 2014Observational
- African ancestry influences CCR5 -2459G>A genotype-associated virologic success of highly active antiretroviral therapy.Journal of acquired immune deficiency syndromes (1999) · 2014Article
- Pharmacogenomics of adverse drug reactions.Genome medicine · 2013Review
Corrections and comments
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Authors and funding
12 authors at 8 institutions in 1 country.
Funding
Abstract
objectiveCYP2B6 variation predicts pharmacokinetic characteristics of its substrates. Consideration for underlying genetic structure is critical to protect against spurious associations with the highly polymorphic CYP2B6 gene.
designThe effect of CYP2B6 variation on response to its substrates, nonnucleoside reverse transcriptase inhibitors (NNRTIs), was explored in the Women's Interagency HIV Study.
methodsFive putative functional polymorphisms were tested for associations with virologic suppression within 1 year after NNRTI initiation in women naive to antiretroviral agents (n = 91). Principal components were generated to control for population substructure. Logistic regression was used to test the joint effect of rs3745274 and rs28399499, which together indicate slow, intermediate, and extensive metabolizers.
resultsRs3745274 was significantly associated with virologic suppression [odds ratio = 3.61, 95% confidence interval (CI) 1.16-11.22, P trend = 0.03]; the remaining polymorphisms tested were not significantly associated with response. Women classified as intermediate and slow metabolizers were 2.90 (95% CI 0.79-12.28) and 13.44 (95% CI 1.66 to infinity) times as likely to achieve virologic suppression compared to extensive metabolizers after adjustment for principal components (P trend = 0.005). Failure to control for genetic ancestry resulted in substantial confounding of the relationship between the metabolizer phenotype and treatment response.
conclusionThe CYP2B6 metabolizer phenotype was significantly associated with virologic response to NNRTIs; this relationship would have been masked by simple adjustment for self-reported ethnicity. Given the appreciable genetic heterogeneity that exists within self-reported ethnicity, these results exemplify the importance of characterizing underlying genetic structure in pharmacogenetic studies. Further follow-up of the CYP2B6 metabolizer phenotype is warranted, given the potential clinical importance of this finding.
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