Genetic Variability of CYP2B6 Polymorphisms in Southeast Iranian Population: Implications for Malaria and HIV/AIDS Treatment

Background: Genetic polymorphisms in the cytochrome P450 2B6 (CYP2B6) gene could infuence therapeutic outcomes of CYP2B6- metabolized drugs such as artemisinin, nevirapine (NVP), and efavirenz (EFV). The main objective of the present study was to analyze the frequency of the most common allele of CYP2B6*1 to *7 and *9 in Iranian Baluchi population and also to compare the frequencies of these polymorphisms with those reported in different ethnic groups. Methods: A total of 206 healthy, unrelated, subjects were participated in this study. CYP2B6*1, *2, *3, *4, *5, *6,*7, and *9 polymorphisms were investigated, using PCR-RFLP followed by sequencing analysis. Results: High frequency of 516T (35.7%) was found among the studied subjects. Also, the three most frequent genotypes were CYP2B6*1/*6 (28.1%), CYP2B6*1/*1 (16%) and CYP2B6*1/*9 (14.6%). The frequency of CYP2B6*6/*6 (4.8%) was not different from Caucasian, Japanese and Chinese populations, but it was lower than West African (17%) and Papua New Guinean (43%) populations. Conclusion: Allele frequencies for CYP2B6 in the examined population were markedly different from those African, Caucasian, and Southeast Asian populations. CYP2B6*2, *4, *5, *6, and *7 were found in the Iranian Baluchi that may affect the response to artemisinin and its derivatives. High frequency of G516T (35.7%) was detected among the examined subjects that might cause greater efavirenz plasma exposure and more central nervous system side effects. Therefore, characterization of pharmacologically relevant polymorphisms in CYP2B6 has a great potential to improve drug efficacy and reduce toxicity.