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Allele and genotype frequencies of the polymorphic cytochrome P450 genes (CYP1A1, CYP3A4, CYP3A5, CYP2C9 and CYP2C19) in the Jordanian population

  • Al Motassem Yousef*
  • , Nailya R. Bulatova
  • , William Newman
  • , Nancy Hakooz
  • , Said Ismail
  • , Hisham Qusa
  • , Farah Zahran
  • , Nidaa Anwar Ababneh
  • , Farah Hasan
  • , Imad Zaloom
  • , Ghada Khayat
  • , Rawan Al-Zmili
  • , Randa Naffa
  • , Ola Al-Diab
  • *Corresponding author for this work
  • University of Jordan
  • University of Manchester

Research output: Contribution to journalArticlepeer-review

Abstract

Drug metabolizing enzymes participate in the neutralizing of xenobiotics and biotransformation of drugs. Human cytochrome P450, particularly CYP1A1, CYP2C9, CYP2C19, CYP3A4 and CYP3A5, play an important role in drug metabolism. The genes encoding the CYP enzymes are polymorphic, and extensive data have shown that certain alleles confer reduced enzymatic function. The goal of this study was to determine the frequencies of important allelic variants of CYP1A1, CYP2C9, CYP2C19, CYP3A4 and CYP3A5 in the Jordanian population and compare them with the frequency in other ethnic groups. Genotyping of CYP1A1(m1 and m2), CYP2C9 (*2 and *3), CYP2C19 ( *2 and *3), CYP3A4*5, CYP3A5 (*3 and *6), was carried out on Jordanian subjects. Different variantsallele were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). CYP1A1 allele frequencies in 290 subjects were 0.764 for CYP1A1*1, 0.165 for CYP1A1*2A and 0.071 for CYP1A1*2C. CYP2C9 allele frequencies in 263 subjects were 0.797 for CYP2C9*1, 0.135 for CYP2C9*2 and 0.068 for CYP2C9*3. For CYP2C19, the frequencies of the wild type (CYP2C19*1) and the nonfunctional (*2 and *3) alleles were 0.877, 0.123 and 0, respectively. Five subjects (3.16 %) were homozygous for *2/*2. Regarding CYP3A4*1B, only 12 subjects out of 173 subjects (6.9 %) were heterozygote with none were mutant for this polymorphism. With respect to CYP3A5, 229 were analyzed, frequencies of CYP3A5*1,*3 and *6 were 0.071, 0.925 and 0.0022, respectively. Comparing our data with that obtained in several Caucasian, African-American and Asian populations, Jordanians are most similar to Caucasians with regard to allelic frequencies of the tested variants of CYP1A1, CYP2C9, CYP2C19, CYP3A4 and CYP3A5.

Original languageEnglish
Pages (from-to)9423-9433
Number of pages11
JournalMolecular Biology Reports
Volume39
Issue number10
DOIs
Publication statusPublished - Oct 2012
Externally publishedYes

Keywords

  • Alleles frequencies
  • CYP450
  • Genotype
  • Jordanian population
  • Polymorphism

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