2012 DEC 24 (NewsRx) -- By a News Reporter-Staff News Editor at AIDS Weekly -- Current study results on Immune System Diseases and Conditions have been published. According to news reporting originating in Torrance, California, by NewsRx journalists, research stated, "Prior candidate gene studies have associated CYP2B6 516G -> T [rs3745274] and 983T -> C [rs28399499] with increased plasma efavirenz exposure. We sought to identify novel variants associated with efavirenz pharmacokinetics."
The news reporters obtained a quote from the research from Los Angeles Biomedical Research Institute, "Antiretroviral therapy-naive AIDS Clinical Trials Group studies A5202, A5095, and ACTG 384 included plasma sampling for efavirenz pharmacokinetics. Log-transformed trough efavirenz concentrations (C-min) were previously estimated by population pharmacokinetic modeling. Stored DNA was genotyped with Illumina HumanHap 650Y or 1MDuo platforms, complemented by additional targeted genotyping of CYP2B6 and CYP2A6 with MassARRAY iPLEX Gold. Associations were identified by linear regression, which included principal component vectors to adjust for genetic ancestry. Among 856 individuals, CYP2B6 516G -> T was associated with efavirenz estimated C-min (P = 8.5 x 10(-41)). After adjusting for CYP2B6 516G -> T, CYP2B6 983T -> C was associated (P = 9.9 x 10(-11)). After adjusting for both CYP2B6 516G -> T and 983T -> C, a CYP2B6 variant (rs4803419) in intron 3 was associated (P = 4.4 x 10(-15)). After adjusting for all the three variants, non-CYP2B6 polymorphisms were associated at P-value less than 5 x 10(-8). In a separate cohort of 240 individuals, only the three CYP2B6 polymorphisms replicated. These three polymorphisms explained 34% of interindividual variability in efavirenz estimated C-min. The extensive metabolizer phenotype was best defined by the absence of all three polymorphisms. Three CYP2B6 polymorphisms were independently associated with efavirenz estimated C-min at genome-wide significance, and explained one-third of interindividual variability."
According to the news reporters, the research concluded: "These data will inform continued efforts to translate pharmacogenomic knowledge into optimal efavirenz utilization."
For more information on this research see: Genome-wide association study of plasma efavirenz pharmacokinetics in AIDS Clinical Trials Group protocols implicates several CYP2B6 variants. Pharmacogenetics and Genomics, 2012;22(12):858-867. Pharmacogenetics and Genomics can be contacted at: Lippincott Williams & Wilkins, 530 Walnut St, Philadelphia, PA 19106-3621, USA. (Lippincott Williams and Wilkins - www.lww.com; Pharmacogenetics and Genomics - journals.lww.com/jpharmacogenetics/pages/default.aspx)
Our news correspondents report that additional information may be obtained by contacting E.R. Holzinger, Harbor UCLA Med Center, Los Angeles Biomed Res Inst, Dept. of Med, Torrance, CA 90509, United States (see also Immune System Diseases and Conditions).
Keywords for this news article include: Pharmaceuticals, Drugs, Therapy, Torrance, Genetics, HIV/AIDS, California, United States, Pharmacokinetics, Clinical Trial Research, North and Central America, Immune System Diseases and Conditions
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