High predictive value of CYP2B6 SNPs for steady-state plasma efavirenz levels in South African HIV/AIDS patients

• DOI: 10.1097/fpc.0b013e328363176f
• Publication Date: 2013-06-15T11:07:01Z
• Authors: Marelize Swart; Michelle Skelton; Yuan Ren; Peter Smith; Simbabrashe Takuva; Collet Dandara
• Keywords: Efavirenz; CYP2B6

Efavirenz is primarily metabolized by CYP2B6, with a minor contribution from CYP1A2, CYP2A6, CYP3A4 and CYP3A5. Genetic variability in these genes contributes towards differences plasma efavirenz concentration, which ultimately leads to either development of adverse drug events or emergence virus resistance. However, the clinical utility validity introducing genotype-assisted dosing not known. The aim this study was therefore evaluate effects 14 single-nucleotide polymorphisms (SNPs) five drug-metabolizing enzyme on steady-state levels South African HIV/AIDS patients as well their validity.HIV/AIDS were recruited Themba Lethu Clinic, at Helen Joseph Hospital, Johannesburg. Blood samples for DNA extraction obtained each participant. PCR/RFLP SNaPshot genotyping used SNPs CYP3A5 among 464 Bantu-speaking Africans. Plasma concentrations measured using LC/MS/MS. Genotypes calculate predictive values. Multivariate analysis select minimal set significant validity.Qualitative quantitative allele frequencies observed when comparing Africans African, Caucasian Asian populations. CYP2B6 516T 785G (*6) 983C (*18) alleles significantly associated high levels. A-G-A-C-C A-T-G-T-C haplotypes (with respect 136A>G; 516G>T; 785A>G; 983T>C; 1459C>T) higher efavirenz, whereas G-G-A-T-C A-G-A-T-C showed lower efavirenz. CYP2B6*1/*6 genotype an increased risk loss follow-up. sensitivity, specificity positive values CYP2B6*6/*6 predicting above 4 µg/ml 46, 97 88%, respectively. improved 49, 100 100%, respectively, CYP1A2 -163A (*1F) NR1I3 8784C/C present.Screening 516G>T SNP has value could be deciding dosage individuals homozygous variant, lead better precision medication.