title: Genetic variability of CYP2B6 polymorphisms in southeast Iranian population: implications for malaria and HIV/AIDS treatment.
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.
  
  
  CONCLUSIONS
  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.affiliation: Malaria and Vector Research Group (MVRG), Biotechnology Research Center (BRC), Pasteur Institute of Iran, Tehran, Iran.zakeris@yahoo.com.
authors.forename: Sedigheh
authors.initials: S
authors.lastname: Zakeri
authors.affiliation: Biology Department, Khatam University, Tehran, Iran.
authors.forename: Nasrin
authors.initials: N
authors.lastname: Amiri
authors.affiliation: Malaria and Vector Research Group (MVRG), Biotechnology Research Center (BRC), Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Sakineh
authors.initials: S
authors.lastname: Pirahmadi
authors.affiliation: Malaria and Vector Research Group (MVRG), Biotechnology Research Center (BRC), Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Navid
authors.initials: N
authors.lastname: Dinparast Djadid
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000378:metabolism / Q000627:therapeutic use*; D000962:Antimalarials / Q000378:metabolism / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D065702:Cytochrome P-450 CYP2B6 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D007492:Iran / Q000453:epidemiology; D008288:Malaria / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D000962:Antimalarials; C585599:CYP2B6 protein, human; D065702:Cytochrome P-450 CYP2B6