Abstract:The main objective of this study was to evaluate CYP2C19 genetic polymorphism in a Saudi Arabian population by determining the frequencies of CYP2C19*2, *3, *4, *6, *7 and *17 alleles and their relevant genotypes. Genomic DNA was isolated from 192 healthy Saudi Arabians, representing different geographical regions, and genotyping of the selected CYP2C19 variants was carried out by direct sequencing after PCR amplification. The allelic frequency of heterozygous CYP2C19*2 was 8.2% with only one individual found to carry the homozygous genotype of this defective allele. None of the other investigated poor metabolizer alleles (i.e. CYP2C19*3, *4, *6 and *7) was detected in the study population. About 46% of the examined volunteers were found to carry CYP2C19*17 genotype (37.5% heterozygous and 8.1% homozygous of the defective allele) with an overall CYP2C19*17 allelic frequency of 26.9%. In addition, a novel CYP2C19 SNP (G356A) and another very rare SNP (C336T) have been identified in this study with a frequency of about 50% for each. Further studies are required to evaluate the metabolic and clinical relevance of CYP2C19*17, G356A and C336T in the Saudi Arabian population.

IntroductionGlucuronidation is an important phase II pathway responsible for the metabolism of many endogenous substances and drugs to less toxic metabolites, which undergo renal excretion. The aim of the current work was to evaluate genotype and allele frequencies of certain UDP-glucuronosyltransferase 1A1 (UGT1A1) variants in an Arab population.Material and methodsGenomic DNA was isolated from 192 healthy unrelated Saudi males of various geographic regions and genotyping of UGT1A1*6, *27, *36, *28, *37, and *60 was carried out using polymerase chain reaction (PCR) amplification followed by direct sequencing.ResultsThe most common allele for (TA) repeats was the wild type (TA)6 with a frequency of 74.3% followed by the mutant (TA)7 (i.e., UGT1A1*28) with a frequency of 25.7%. The distribution of UGT1A1*60 allele was 62.4% among subjects with the homozygous mutant genotype of 35.4%, while the wild type variant represents 10.6% only. Both UGT1A1*6 and *27 were not detected as all screened subjects showed a homozygous wild type pattern. Similarly, UGT1A1*36* and *37 were either not present or rarely found, respectively. In comparison to other populations, the frequency of UGT1A1*60 and *28 in the studied population was less than that of African Americans but higher than Asians. The geographical origin of the study subjects also implied some differences in genotype distribution of (TA) repeats and UGT1A1*60.ConclusionsOur data indicate that Saudis harbor some important UGT1A1 mutations known to affect enzyme activity. Additional studies are warranted to assess the clinical implications of these gene polymorphisms in this ethnic group.

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Polymorphisms in multidrug resistance (MDR1) gene play an important role in influencing the pharmacological action and toxicity profile of a large number of therapeutic agents, and in human susceptibility to various diseases. Because of genotypic variability, several studies were directed toward determination of the frequencies of MDR1 polymorphisms and/or haplotypes in different ethnic populations. In this study, we determined the frequencies of the most common three polymorphisms in the MDR1 gene (i.e., C1236T, G2677T, and C3435T) in Saudi Arabians and their haplotypes. Our results showed that the frequencies of 1236T, 2677T, and 3435T were 43.7 %, 40.2 %, and 42.2 %, respectively. In addition, the frequencies of the most common MDR1 haplotypes, C-G-C and T-T-T, were correspondent to 48.8 and 35.5 %. Furthermore, we identified moderate to strong linkage disequilibrium between the loci of these single nucleotide polymorphisms in the studied subjects. These identified frequencies in Saudi Arabians are different from that reported in the other ethnic groups.

This erratum is published as one of the author's surname was incorrectly published. Mohammad Khalid Parvez should be read as M. K. Parvez.