Frequencies of three CYP2D6 nonfunctional alleles (CYP2D6*3, *4, and *6) within an Iranian population (Mazandaran).

Although the frequencies of CYP2D6 nonfunctional alleles have been extensively studied in most populations worldwide, limited information is available for those of the Iranian population. The present study aimed to determine the frequency of three CYP2D6 nonfunctional alleles (CYP2D6*3, *4, and *6) in the Mazandarani ethnic group among the Iranian population. A total of 100 unrelated healthy subjects living in Mazandaran, a Caspian province in the north of Iran, were selected. Lymphocytic genomic DNA was genotyped by a polymerase chain reaction amplification method for detection of three nonfunctional alleles. Finally, the obtained data were used to determine the frequencies of the three alleles, and the results were compared with published data from other populations. The frequencies for CYP2D6 alleles *3, *4, and *6 were 0.5%, 9%, and 0.5%, respectively. Homozygous or compound heterozygous genotypes that predict poor metabolizer phenotype, that is, *4/*4 or *4/*6, were not found in this study. The result of the present study showed that CYP2D6*4 is the major nonfunctional allele found in Mazandarani subjects. In addition, the three inactive alleles of CYP2D6 accounted for 10% of CYP2D6 alleles in our sample versus 0.2%-25.2% reported in other populations. The frequencies of the studied alleles resulted in significant differences between our sample and East Asians, Black-Tanzanians, Saudi Arabians, and Caucasians.

Metabolic capacity of CYP2D6 within an Iranian population (Mazandaran Province).

BACKGROUND: CYP2D6 is polymorphically expressed enzyme that show marked interindividual and interethnic variation. Phenotyping of CYP2D6 provides valuable information about real-time activity of this important drug-metabolizing enzymes through the use of specific probe drugs. The aim of this study was to identify the CYP2D6 oxidation phenotype with dextromethorphan (DEX) as a probe drug in Mazandarani ethnic group among Iranian population. METHODS: The study included 71 unrelated healthy volunteers. Dextromethorphan hydrobromide (30 mg) was given orally to healthy subjects and peripheral venous blood samples (10 ml) were taken at 3 hr post-dose. Dextromethorphan and the metabolite dextrorphan (DOR) were analyzed by the HPLC method. The log DEX/DOR metabolic ratio (MR) at 3 hr plasma sample was used as the index of CYP2D6 activity and a value of 0.3 was used as the antimode separating extensive metabolizers (EM) and poor metabolizers (PM) phenotypes. RESULTS: A 560-fold interindividual variation in dextromethorphan MRs was observed in this study. Considering the antimode 0.3 in log scale, 7.04% (5/71) volunteers were identified as PMs. Conclusion : The result showed that the frequency of CYP2D6 PM phenotypes accounted for 7.04% of subjects in our samples. Despite these findings, we propose a further study in larger samples to provide a wider image and to get more valuable information upon pharmacogenetic basis for individual therapy and personalized medicine.