Sedigheh Zakeri1, Nasrin Amiri2, Sakineh Pirahmadi3, Navid Dinparast Djadid3. 1. Malaria and Vector Research Group (MVRG), Biotechnology Research Center (BRC), Pasteur Institute of Iran, Tehran, Iran.zakeris@yahoo.com. 2. Biology Department, Khatam University, Tehran, Iran. 3. Malaria and Vector Research Group (MVRG), Biotechnology Research Center (BRC), Pasteur Institute of Iran, Tehran, Iran.
Abstract
BACKGROUND: Genetic polymorphisms in the cytochrome P450 2B6 (CYP2B6) gene could influence 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 artemisin 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.
BACKGROUND: Genetic polymorphisms in the cytochrome P450 2B6 (CYP2B6) gene could influence 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 artemisin 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.
Authors: Jen Fuk Liem; Dwi A Suryandari; Safarina G Malik; Muchtaruddin Mansyur; Dewi S Soemarko; Aria Kekalih; Imam Subekti; Franciscus D Suyatna; Bertha Pangaribuan Journal: J Prev Med Public Health Date: 2022-05-16
Authors: Linawati Hananta; Indwiani Astuti; Ahmad Hamim Sadewa; Josephine Alice; Jontari Hutagalung Journal: Osong Public Health Res Perspect Date: 2018-08
Authors: Immaculate M Langmia; Katja S Just; Sabrina Yamoune; Jürgen Brockmöller; Collen Masimirembwa; Julia C Stingl Journal: Front Genet Date: 2021-07-12 Impact factor: 4.599