Prevalence of the CYP 2B6 516 G>T and 983 T>C Polymorphisms and Association with the Development of Adverse Drug Reactions Among HIV/AIDS Patients in Yaounde, Cameroon

Identification: Nguefeu Nkenfou, Carine


Prevalence of the CYP 2B6 516 G>T and 983 T>C Polymorphisms and Association with the Development of Adverse Drug Reactions Among HIV/AIDS Patients in Yaounde, Cameroon
Carine Nguefeu Nkenfou1,2, Barbara Atogho Tiedeu1,2, Celine Nguefeu Nkenfou 3,4,5 ,Akindeh M. Nji1,2, Jean Paul Chedjou1,2, Calvino Tah Fomboh2, Charles Nkouanfack6, and Wilfred Fon Mbacham1,2,7  
1University 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;  4Higher Teachers' Training College, University of Yaoundé I, Cameroon; 5Molecular Biology Center Yaoundé, Cameroon; 6Central Hospital Yaoundé, Cameroon; 7University of Yaoundé I, Cameroon
It has been recognized for more than 50 years that genetic differences among people contribute to inter-individual differences in the response to treatment. Cytochrome P450 (CYP) 2B6 is an important hepatic isoenzyme responsible for the metabolism of non nucleosidereverse transcriptase inhibitors (NNRTIs) including Efavirenz (EFV) and Nevirapine (NVP) used in the treatment of HIV/AIDS. The CYP2B6 gene 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). The aim of this study was to determine the prevalence of the CYP 2B6 516 G>T and 983 T>C polymorphisms and investigate their association with the development of adverse drugs reactions among HIV patients in Cameroon where HIV/AIDS still pose a significant public health problem. 
The study received an approval from the National Health Bioethics Committee of Cameroon. Patients consent was obtained prior blood samples collection. A repertoire of patients with and without adverse drug reactions was constituted after 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 by chelex method. PCR-RFLP was performed with restriction enzymes BSrI and BSmAI for detection of CYP 2B6 SNPs. All data was entered on SPSS version 16.0 (SPSS Inc., USA) statistical software. 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. The association between genotype and adverse effects of ART in the study population was assessed by binary logistic regression analysis.
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. Allele frequencies for the CYP2B6 516G>T SNP were 40.96% for G allele and 59.04% for C allele and allele frequencies for the CYP2B6 983T>C SNP were 94.4% for T allele and 5.6% for C allele. Association analysis revealed that homozygotes for the wild type allele (516GG) were likely to have some degree of protection against ADR susceptibility with a statistically significant difference (OR=0.885, P=0.029). For CYP2B6 T983C SNP we observed that 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).
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. These data may have implications for administration of non nucleoside reverse transcrptase inhibitors to Cameroonian patients.


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