Allele and genotype frequencies of polymorphic cytochromes P450 (CYP2C9, CYP2C19, CYP2E1) and dihydropyrimidine dehydrogenase (DPYD) in the Egyptian population

Abstract

Aims The goal of this study was to determine the frequencies of important allelic variants of CYP2C9, CYP2C19, CYP2E1 and DPYD in the Egyptian population and compare them with the frequencies in other ethnic populations. Methods Genotyping of CYP2C9 (*2 and *3), CYP2C19 (*2 and *3), c2 variant of CYP2E1 and DPYD alleles (*2 A-*6 ) was carried out in a total of 247 unrelated Egyptian subjects. An allele-specific fluorogenic 5k nuclease chain reaction assay was applied for detection of CYP2C9 and CYP2C19 variants. Other variants of the CYP2E1 and DPYD genes were determined using polymerase chain reaction (PCR)-restriction fragment length polymorphism and allele-specific PCR based assays. Results CYP2C9 allele frequencies in 247 Egyptian subjects were 0.820 for CYP2C9*1, 0.120 for CYP2C9*2 and 0.060 for CYP2C9*3. For CYP2C19, the frequencies of the wild type (CYP2C19*1) and the nonfunctional (*2 and *3) alleles were 0.888, 0.110 and 0.002, respectively. CYP2C19*3, which is considered an Asian mutation, was detected in one subject (0.40%) who was heterozygous (*1/*3). Two subjects (0.80%) were homozygous for *2/*2, while no compound heterozygotes (*2/*3) or homozygotes for *3 were detected. For CYP2E1, only four subjects (1.70%) had the rare c2 variant, expressed heterozygously, giving an allele frequency of 0.009. Five variants of DPYD were analysed, with no splice sites (*2 A) or DC1897 (*3) found in this population. The frequencies of other variants were 0.028, 0.115 and 0.090 for *4, *5 and *6, respectively. Conclusions Comparing our data with that obtained in several Caucasian, AfricanAmerican and Asian populations, we found that Egyptians resemble Caucasians with regard to allelic frequencies of the tested variants of CYP2C9, CYP2C19, CYP2E1 and DPYD. Our results may help in better understanding the molecular basis underlying ethnic differences in drug response, and contribute to improved individualization of drug therapy in the Egyptian population.

Testing for variants in CYP2C19: population frequencies and testing experience in a clinical laboratory

“…These include Brazil, 35 Iran, 36,37 East Asia, 38 Ghana, 39 United States Ashkenazi Jews, 40 Greece, 41 Mexican Americans, 42 Bolivia, 43 Israel, 44 Malaysia, 45 Egypt, 46 and whites of European descent. 47 However, these studies were limited to a small number of deficiency alleles and did not include the *17 gain-of-function allele.…”

Use of Pyrosequencing to Detect Clinically Relevant Polymorphisms in Dihydropyrimidine Dehydrogenase

“…In addition, in their study of 478 Egyptians, Hamdy et al (18 ) reported a frequency of 11.5% for DPYD*5, which is between the frequencies for the Caucasian (19%) and sub-Saharan African populations (9%) found in this study. For DPYD*6, the reported frequency for the Egyptian population (9%) is higher than the frequency found in both the Caucasian (5%) and sub-Saharan African (4%) populations (18 ). In a study on 100 Japanese individuals, Wei et al (12 ) reported frequencies of 35.2% for DPYD*5 and 4.4% for DPYD*6.…”

A Survey on the Prevalence of IVS14 + 1G > A Mutation of the Dihydropyrimidine Dehydrogenase Gene Among a Group of Colorectal Cancer Patients in Northeast Iran, the Relevance of Fluoropyrimidine Based Chemotherapy Toxicity

“…From Egypt, a study comprised of 247 healthy individuals reported no referred DPD IVS14 + 1G > A mutation (16). In an analysis of DPD mutations, among 300 Taiwanese healthy subjects the researchers found no mutation of IVS14 + 1G > A.…”