Dataset Information

Genotyping of CYP2C9 and VKORC1 in the Arabic population of Al-Ahsa, Saudi Arabia.

ABSTRACT: Polymorphisms in the genes encoding CYP2C9 enzyme and VKORC1 reductase significantly influence the dose variability of coumarinic oral anticoagulants (COAs). Substantial inter- and intraethnic variability exists in the frequencies of CYP2C9*2 and *3 and VKORC1 -1639A alleles. However, the prevalence of CYP2C9 and VKORC1 genetic variants is less characterized in Arab populations. A total of 131 healthy adult subjects from the Al-Ahsa region of Saudi Arabia were genotyped for the CYP2C9 *2 and *3 and VKORC1 -1639G>A polymorphisms by PCR-RFLP method. The frequencies of the CYP2C9 *2 and *3 and VKORC1 -1639A alleles were 13.3%, 2.3%, and 42.4%, respectively, with no subjects carrying 2 defective alleles. The frequencies of the CYP2C9 *3 and VKORC1 -1639A alleles were significantly lower than those reported in different Arabian populations. None of the subjects with the VKORC1 -1639AA genotype were carriers of CYP2C9 *1/*3 genotypes that lead to sensitivity to COAs therapy. The low frequency of the CYP2C9 *3 allele combined with the absence of subjects carrying 2 defective CYP2C9 alleles suggests that, in this specific population, pharmacogenetic COAs dosing may mostly rely upon VKORC1 genotyping.

SUBMITTER: Alzahrani AM

PROVIDER: S-EPMC3613048 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Genotyping of CYP2C9 and VKORC1 in the Arabic population of Al-Ahsa, Saudi Arabia.

Alzahrani Abdullah M AM Ragia Georgia G Hanieh Hamza H Manolopoulos Vangelis G VG

BioMed research international 20130317

Polymorphisms in the genes encoding CYP2C9 enzyme and VKORC1 reductase significantly influence the dose variability of coumarinic oral anticoagulants (COAs). Substantial inter- and intraethnic variability exists in the frequencies of CYP2C9*2 and *3 and VKORC1 -1639A alleles. However, the prevalence of CYP2C9 and VKORC1 genetic variants is less characterized in Arab populations. A total of 131 healthy adult subjects from the Al-Ahsa region of Saudi Arabia were genotyped for the CYP2C9 *2 and *3 ...[more]

PMID: 23586031

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Project description:One of the well-studied phase II drug metabolizing enzymes is N-acetyltransferase 2 (NAT2) which has an essential role in the detoxification and metabolism of several environmental toxicants and many therapeutic drugs like isoniazid (antituberculosis, TB) and antimicrobial sulfonamides. According to the variability in the acetylation rate among different ethnic groups, individuals could be classified into slow, intermediate, and fast acetylators; these variabilities in the acetylation rate are a result of single nucleotide polymorphisms (SNPs) in the coding sequence of NAT2. The variety of NAT2 acetylation status is associated with some diseases such as bladder cancer, colorectal cancer, rheumatoid arthritis, and diabetes mellitus. The main objectives of this research are to describe the genetic profile of NAT2 gene among the people of the Al-Ahsa region, to detect the significant SNPs of this gene, to determine the frequency of major NAT2 alleles and genotypes, and then categorize them into fast, intermediate, and slow acetylators. Blood samples were randomly collected from 96 unrelated people from Al-Ahsa population, followed by DNA extraction then amplifying the NAT2 gene by polymerase chain reaction (PCR); finally, functional NAT2 gene (exon 2) was sequenced using the Sanger sequencing method. The well-known seven genetic variants of NAT2 gene are 191G>A, 282C>T, 341T>C, 481C>T, 590G>A, 803A>G, and 857G>A were detected with allele frequencies 1%, 35.4%, 42.7%, 41.1%, 29.2%, 51%, and 5.7%, respectively. The most common NAT2 genetic variant among Al-Ahsa population was 803A>G with a high frequency 0.510 (95% confidence interval 0.44-0.581) followed by 341T>C 0.427 (95% confidence interval 0.357-0.497). The most frequent two haplotypes of NAT2 were NAT2∗6C (25.00%) and NAT2∗5A (22.92%) which were classified as a slow acetylators. According to trimodal distribution of acetylation activity, the predicted phenotype of Al-Ahsa population was found to be 5.21% rapid acetylators, 34.38% intermediate acetylators, and 60.42% were slow acetylators. In addition, this study found four novel haplotypes NAT2∗5TB, NAT2∗5AB, NAT2∗5ZA, and NAT2∗6W which were slow acetylators. This study revealed a high frequency of the NAT2 gene with slow acetylators (60.42%) in Al-Ahsa population, which might alter the drug's efficacy and vulnerability to some diseases.

Dataset Information

Genotyping of CYP2C9 and VKORC1 in the Arabic population of Al-Ahsa, Saudi Arabia.

Publications

Genotyping of CYP2C9 and VKORC1 in the Arabic population of Al-Ahsa, Saudi Arabia.

Similar Datasets

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