Frequency of certain single-nucleotide polymorphisms and duplication of CYP2D6 in the Jordanian population.
The CYP2D6 isozymes are responsible for metabolism of 7-10% of clinically available drugs. Genetic polymorphism in CYP2D6 may have an impact on drug efficacy and toxicity. The aim of this study was to determine the allelic frequency of CYP2D6*4, *10, and *17 and CYP2D6*2×N duplication allele in 192 healthy unrelated male and female Jordanian volunteers. Polymerase chain reaction (PCR)-restriction fragment length polymorphism-based methods were used to identify the CYP2D6*4, *10, and *17 genotypes; and allele-specific long PCR was used to determine the CYP2D6*2×N allelic frequency. The CYP2D6*10 allele was the most frequent mutant allele in Jordanians (14.8%) followed by CYP2D6*4 and *17 at 12.8%, and 8.3%, respectively. The duplication allele was found in 13.5% of the studied sample. The CYP2D6*4 G-A heterozygote genotype frequency was 20.3%, and the homozygous mutant genotype was 2.6%. In case of CYP2D6*10 C-T and CYP2D6*17 G-C heterozygote genotypes, the frequencies were 21.4% and 12.5%, respectively, while the homozygous mutant genotype frequencies of T-T and C-C were 4.2% and 2.1%, respectively. In conclusion, the allelic distributions of the CYP2D6 gene among Jordanians are different from other Mediterranean groups, especially the *10 and *17 single-nucleotide polymorphisms, and more importantly the CYP2D6*2×N duplication allele, which seems to follow a gradient reduction in prevalence from Ethiopia to Northern Europe.
Department of Pharmacology, University of Jordan, Amman, Jordan. m.zihlif@ju.edu.jo
Malek
M
Zihlif
Amer
A
Imraish
Yacoub M
YM
Irshaid
D000328:Adult; D044466:Asian People / Q000235:genetics*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D005260:Female; D020440:Gene Duplication; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007597:Jordan; D008297:Male; D009154:Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide
D019389:Cytochrome P-450 CYP2D6