title: Pharmacogenetic markers of CYP2B6 associated with efavirenz plasma concentrations in HIV-1 infected Thai adults.
abstract: OBJECTIVE
  To investigate the frequency of CYP2B6 polymorphisms and the influence of haplotype structure on plasma efavirenz concentrations in Thai adults with HIV-1 infection.
  
  
  METHODS
  Genotyping of nine single nucleotide polymorphisms (SNPs, c.64C>T, c.499C>G, c.516G>T, c.785A>G, c.1375A>G, c.1459C>T, g.3003T>C, g.18492C>T and g.21563C>T) of CYP2B6 were performed using real-time PCR-based allelic discrimination on blood samples from 52 HIV-infected adults who had received an efavirenz-based regimen. Plasma efavirenz concentrations were measured by high performance liquid chromatography.
  
  
  RESULTS
  The minor allele frequencies for c.64C>T, c.516G>T, c.785A>G, g.3003C>T, g.18492T>C and g.21563C>T were 0.087, 0.365, 0.413, 0.308 and 0.356, respectively. However, no variant alleles were identified for three SNPs (c.499 C>G, c.1375 A>G and c.1459 C>T). Efavirenz plasma concentrations were significantly associated with c.516G>T (P= 0.0095), c.785A>G (P= 0.0017), g.21563C>T (P= 0.0036) and g.18492C>T (P= 0.0011). The composite CYP2B6 of three SNPs (c.516G ≥ T, c.785A ≥ G and g.21563C ≥ T) genotypes were significantly associated with higher efavirenz concentrations.
  
  
  CONCLUSIONS
  Our data indicate that the GAC-CYP2B6 haplotype is associated with higher plasma efavirenz concentrations in HIV-infected Thai adults.
authors.affiliation: Laboratory for Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. racska@mahidol.ac.th
authors.forename: Chonlaphat
authors.initials: C
authors.lastname: Sukasem
authors.forename: Tim R
authors.initials: TR
authors.lastname: Cressey
authors.forename: Pattamawan
authors.initials: P
authors.lastname: Prapaithong
authors.forename: Yardpiroon
authors.initials: Y
authors.lastname: Tawon
authors.forename: Ekawat
authors.initials: E
authors.lastname: Pasomsub
authors.forename: Chutatip
authors.initials: C
authors.lastname: Srichunrusami
authors.forename: Thawinee
authors.initials: T
authors.lastname: Jantararoungtong
authors.forename: Marc
authors.initials: M
authors.lastname: Lallement
authors.forename: Wasun
authors.initials: W
authors.lastname: Chantratita
mesh_terms: D000293:Adolescent; D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000493:pharmacokinetics*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D048588:Benzoxazines / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D003521:Cyclopropanes; D065702:Cytochrome P-450 CYP2B6; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics*; D010597:Pharmacogenetics; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D013785:Thailand; D055815:Young Adult
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D005819:Genetic Markers; D001189:Aryl Hydrocarbon Hydroxylases; C585599:CYP2B6 protein, human; D065702:Cytochrome P-450 CYP2B6; D010089:Oxidoreductases, N-Demethylating; C098320:efavirenz