title: CYP2B6 poor metaboliser alleles involved in efavirenz and nevirapine metabolism: CYP2B6*9 and CYP2B6*18 distribution in HIV-exposed subjects from Dschang, Western Cameroon.
abstract: The prescription of patients' tailored anti-infectious treatments is the ultimate goal of pharmacogenetics/genomics applied to antimicrobial treatments, providing a basis for personalized medicine. Despite the efforts to screen Africans for alleles underlying defective metabolism for a panel of different drugs, still more research is necessary to clarify the interplay between host genetic variation and treatments' response. HIV is a major infectious disease in sub-Saharan African countries, and the main prescribed anti-HIV combination therapy includes efavirenz (EFV) or nevirapine (NVP). The two drugs are both mainly metabolised by cytochrome P450 2B6 liver enzyme (CYP2B6). Defective variants of CYP2B6 gene, leading to higher drug exposure with subsequent possible side effects and low compliance, are well known. However, little is known about CYP2B6 alleles in Cameroon where only one study was done on this subject. The main objective of the present work is to assess, in a subset of HIV-exposed subjects from Dschang in West Cameroon, the prevalence of two SNPs in the CYP2B6 gene: 516G>T (rs3745274) and 983T>C (rs28399499), both associated to a defective EFV and NVP metabolism. We analyzed 168 DNA samples collected during two cross-sectional surveys performed in Dschang, West Cameroon. In the population studied the observed allele frequencies of 516G>T and 983T>C were 44.35% (95%CI, 36.84-51.86%) and 12.80% (95%CI, 7.75-17.85%), respectively. Moreover, concerning the CYP2B6 expected phenotypes, 28.57% of the population showed a poor metaboliser phenotype, while 27.38% and 44.05% showed an extensive (wild-type) and an intermediate metaboliser phenotype, respectively. Here we found that an important fraction of the subjects is carrying EFV/NVP poor metaboliser alleles. Our findings could help to improve the knowledge about the previewed efficacy of anti-HIV drug therapy in Cameroon. Finally, we designed a new method of detection for the 983T>C genetic variation that can be applied in resource-limited laboratories.
authors.affiliation: University of Botswana-University of Pennsylvania Partnership, Gaborone, Botswana; Medical Education Partnership Initiative (MEPI) Laboratory, Gaborone, Botswana; Department of Public Health and Infectious Diseases, "Sapienza" University of Rome, Rome, Italy. Electronic address: paganottig@botswana-upenn.co.bw.
authors.forename: Giacomo Maria
authors.initials: GM
authors.lastname: Paganotti
authors.affiliation: Department of Public Health and Infectious Diseases, "Sapienza" University of Rome, Rome, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Russo
authors.affiliation: Biomedical Sciences Department, Faculty of Sciences, University of Dschang, Dschang, Cameroon.
authors.forename: Martin Sanou
authors.initials: MS
authors.lastname: Sobze
authors.affiliation: District Hospital of Dschang, Dschang, Cameroon.
authors.forename: George Bouting
authors.initials: GB
authors.lastname: Mayaka
authors.affiliation: University of Botswana-University of Pennsylvania Partnership, Gaborone, Botswana; Medical Education Partnership Initiative (MEPI) Laboratory, Gaborone, Botswana.
authors.forename: Charles Waithaka
authors.initials: CW
authors.lastname: Muthoga
authors.affiliation: University of Botswana-University of Pennsylvania Partnership, Gaborone, Botswana; Medical Education Partnership Initiative (MEPI) Laboratory, Gaborone, Botswana.
authors.forename: Leabaneng
authors.initials: L
authors.lastname: Tawe
authors.affiliation: Wellcome Trust Genome Campus, Hinxton, UK.
authors.forename: Axel
authors.initials: A
authors.lastname: Martinelli
authors.affiliation: Department of Public Health and Infectious Diseases, "Sapienza" University of Rome, Rome, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Romano
authors.affiliation: Department of Public Health and Infectious Diseases, "Sapienza" University of Rome, Rome, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Vullo
mesh_terms: D000293:Adolescent; D000328:Adult; D000480:Alkynes; D048588:Benzoxazines / Q000493:pharmacokinetics* / Q000627:therapeutic use; D044383:Black People / Q000235:genetics*; D002163:Cameroon; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D003521:Cyclopropanes; D065702:Cytochrome P-450 CYP2B6 / Q000235:genetics*; D005787:Gene Frequency; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D007223:Infant; D019829:Nevirapine / Q000493:pharmacokinetics* / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D057285:Precision Medicine; D055815:Young Adult
chemical_list: D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D019829:Nevirapine; C585599:CYP2B6 protein, human; D065702:Cytochrome P-450 CYP2B6; C098320:efavirenz
keywords: CYP2B6; Cameroon; Efavirenz; Nevirapine; Pharmacogenetics; Poor metabolisers