title: Genetic variants of drug metabolizing enzymes and drug transporter (ABCB1) as possible biomarkers for adverse drug reactions in an HIV/AIDS cohort in Zimbabwe.
abstract: A study was conducted in an HIV/AIDS Zimbabwean cohort to assess possible associations of pharmacogenetic variants with common adverse drug reactions (ADRs) during anti-retroviral treatment (ART) and/or tuberculosis (TB) treatment. Genotype and allele frequencies for CYP2B6 G516T, CYP2B6 T983C, CYP2A6*17, ABCB1 rs10276036 C>T, NAT2*5 and NAT2*14 were similar to those reported in literature for other African populations. The CYP2B6 516TT genotype and male gender were significantly associated with occurrence of Efavirenz induced central nervous system disorders (OR 20.58, p=0.004) and the ABCB1 rs10276036TT genotype with Nevirapine induced skin hypersensitivity (OR 4.01, p=0.04). For Stavudine, time on treatment was the main factor in development of lipodystrophy (OR 1.06, p<0.0001). For isoniazid, increasing patient age was associated with peripheral neuropathy (OR 1.05, p=0.001). Although genetic polymorphisms may play a role in predicting occurrence of ADRs, this study also indicates that other factors (gender, age, treatment time) are crucial in predicting drug-induced adverse effects.
authors: Milcah
authors: M
authors: Dhoro
authors: Bernard
authors: B
authors: Ngara
authors: Gerald
authors: G
authors: Kadzirange
authors: Charles
authors: C
authors: Nhachi
authors: Department of Molecular Sciences, African Institute of Biomedical Science & Technology, Dominion House, 211 Herbert Chitepo and Sam Nujoma Street, Harare, Zimbabwe. milcah.dhoro@aibst.com.
authors: Collen
authors: C
authors: Masimirembwa
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D044966:Anti-Retroviral Agents / Q000009:adverse effects; D000995:Antitubercular Agents / Q000009:adverse effects; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D016022:Case-Control Studies; D004342:Drug Hypersensitivity / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012044:Regression Analysis; D012307:Risk Factors; D015030:Zimbabwe
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D044966:Anti-Retroviral Agents; D000995:Antitubercular Agents; D005819:Genetic Markers; D001189:Aryl Hydrocarbon Hydroxylases; D001191:Arylamine N-Acetyltransferase