title: Slow acetylator phenotype and genotype in HIV-positive patients with sulphamethoxazole hypersensitivity.
abstract: OBJECTIVE
  To test the role of acetylator status, and to investigate the reported discrepancy between acetylator phenotype and genotype in HIV-positive patients with sulphamethoxazole (SMX) hypersensitivity.
  
  
  METHODS
  Forty HIV-positive patients (32 of whom were SMX-hypersensitive), and 26 healthy volunteers, were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis, and phenotyped using dapsone (50 mg) as a probe, for acetylator status. Sequencing of the NAT2 exon was performed where discrepancy between phenotyping and genotyping was detected. Our results were also pooled with published studies addressing slow acetylator status in HIV-positive SMX-hypersensitive patients.
  
  
  RESULTS
  Slow acetylator genotype and phenotype frequencies did not differ between HIV-positive SMX-hypersensitive and nonhypersensitive patients, and healthy controls, which was further confirmed in a meta-analysis of published studies (pooled odds ratio 2.25, 95% confidence interval 0.45, 11.17). Discordance between phenotype and genotype was resolved in four of the subjects by sequencing of the whole NAT2 exon, which revealed rare mutations, leaving three (9%) HIV-positive SMX-hypersensitive patients and one (4%) healthy volunteer who continued to demonstrate the discordance.
  
  
  CONCLUSIONS
  Slow acetylator phenotype or genotype is unlikely to predispose to SMX hypersensitivity in HIV-positive patients, although a minor role cannot be excluded. Phenotype-genotype discrepancies are partly due to nondetection of all rare alleles by PCR methodology, and can be circumvented by sequencing of the gene in patients showing a discrepancy.
authors.affiliation: Department of Pharmacology and Therapeutics, The University of Liverpool, Liverpool, UK.
authors.forename: Ana
authors.initials: A
authors.lastname: Alfirevic
authors.forename: Anne C
authors.initials: AC
authors.lastname: Stalford
authors.forename: F Javier
authors.initials: FJ
authors.lastname: Vilar
authors.forename: Ed G L
authors.initials: EG
authors.lastname: Wilkins
authors.forename: B Kevin
authors.initials: BK
authors.lastname: Park
authors.forename: Munir
authors.initials: M
authors.lastname: Pirmohamed
mesh_terms: D000107:Acetylation / Q000187:drug effects*; D000328:Adult; D004342:Drug Hypersensitivity / Q000235:genetics*; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008875:Middle Aged; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D013420:Sulfamethoxazole / Q000627:therapeutic use*
chemical_list: D013420:Sulfamethoxazole