Frequency of Certain Single-Nucleotide Polymorphisms and Duplication ofCYP2D6in the Jordanian Population

Abstract

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.