Carine NGUEFEU NKENFOU1,2*, Barbara ATOGHO TIEDEU1,2 , Celine NGUEFEU NKENFOU3,4,5 , Akindeh MBU NJI1,2 , Jean Paul CHEDJOU1,2 , Calvino TAH FOMBOH2 , Charles KOUANFACK6 , Wilfred FON MBACHAM1,2
1Faculty of Science, University of Yaoundé I, Cameroon ; 2The Biotechnology Center, University of Yaoundé I, Yaoundé, Cameroon ; 3Chantal Biya International Reference Centre for Research on HIV/AIDS Prevention and Management (CBIRC), Yaoundé, Cameroon ; 4 Higher Teachers' Training College, University of Yaoundé I, Cameroon ; 5Molecular Biology Center Yaoundé, Cameroon ; 6Central Hospital Yaoundé, Cameroon
CaHReF 2018, Yaoundé Congres hall, 08 – 11 January 2019 , OAU049
Background: The CYP2B6 gene involved in the metabolism of many drugs including ARV is known to be highly polymorphic and two Single Nucleotide Polymorphisms (SNPs) have been reported to commonly affect the metabolism of both NVP and EFV and thus associated to the development of adverse drug reactions (ADR).
Objectif: To determine the prevalence of the CYP 2B6 516 G>T and 983 T>C polymorphisms and investigate their association with development of ADR among HIV patients
Methodology: A repertoire of patients with and without adverse drug reactions was constituted after the screening of clinical records. They were further contacted by phone calls and those who agreed to participate provided blood samples. The blood was spotted on filter paper for DNA extraction using chelex method. PCR-RFLP was performed with restriction enzymes BSrI and BSmAI for detection of CYP 2B6 SNPs. Genotypes frequencies were compared between participants with or without adverse drug reactions. Frequency of the CYP 2B6 allele and genotypes in the study population was performed by descriptive statistics. Association was assessed by binary logistic regression analysis.
Results: The prevalence of extensive, intermediate and slow metabolizers was 8.2% GG, 65.6% GT and 26.2% TT respectively for the 516G>T and 89.3% TT, 4.1% CT and 6.6% CC respectively for the 983T>C polymorphism. Association analysis revealed that homozygotes for the wild type allele (516GG) were likely to have some degree of protection against ADR with a statistically significant difference (OR=0.885, P=0.029). For CYP2B6 T983C SNP, homozygotes mutant (CC) have about a threefold higher risk to develop adverse reactions (OR=2.677) although the difference did not reach significance (P=0.164).
Conclusion/Recommandation: The results of this study showed that genetic variability in the metabolizing enzyme CYP 2B6 can be involved in adverse drug reactions susceptibility among HIV/AIDS patients under ART. Genotyping for this gene may guide on the better administration of non nucleoside reverse transcriptase inhibitors to Cameroonian patients.
Key Words: Pharmacogenetics; ADR; Association; Cyp2B6 Polymorphisms.