Characterization of drug-metabolizing enzymes CYP2C9, CYP2C19 polymorphisms in Tunisian, Kuwaiti and Bahraini populations

Abdelhédi, Rania; Bouayed, Nouha; AlFadhli, Suad; Abid, Leïla; Rebai, Ahmed; Kharrat, Najla

doi:10.1007/s12041-015-0581-2

Cited by 11 publications

(5 citation statements)

References 19 publications

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“…23 Several studies revealed significant inter-ethnic differences in CYP2C19*2 variants. Approximately similar inferences of our results were reported among Beninese population 24 and Zimbabwean population, 25 but less frequency occurred among Ghanaian population (6%), 26 Tunisian population (9%), 27 and Egyptians (4%). 28 Significantly higher frequencies were reported among Japanese (19-23%), Chinese (15%), and Koreans (13%).…”

Section: Discussionsupporting

confidence: 91%

Detection of CYP2C19*2_ allele among Helicobacter pylori -infected patients in two tertiary hospitals of Khartoum, Sudan, 2019

et al. 2021

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Background: CYP2C19*2 has been identified as the most common allelic variant of CYP2C19 affecting the response to Proton pump inhibitors (PPI). This study aims to detect CYP2C19*2 allele in H. pylori-infected Sudanese population, owing its probable effect on H. pylori eradication. Methods: Antral biopsies was collected from 30 patients attending endoscopy units. Extraction of DNA was performed through QIAamp® DNA Mini Kit. Samples were screened for Urease C (UreC) gene of H. pylori using conventional PCR. Detection of CYP2C19*2 was performed in positive H. pylori samples using Real time-PCR. Results: The mean age of patients was 40.7 (±20.2 SE). Positive samples for UreC were 24 (80%) samples. Among them, four samples (16.6%) were found positive for CYP2C19*2 allele presence. Gender was found to be statistically associated with the presence of the allele (p < 0.05). Conclusion: This study illustrates that CYP2C19*2 is of modest prevalence among H. pylori-infected Sudanese population. The determination of genotypic and allelic frequencies of CYP2C19 gene among different populations will provide data to be used to personalize treatment according to individual genetic profile, and minimize the possible adverse side effects of CYP2C19 substrates.

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Section: Discussionsupporting

confidence: 91%

Detection of CYP2C19*2_ allele among Helicobacter pylori -infected patients in two tertiary hospitals of Khartoum, Sudan, 2019

et al. 2021

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“…The great divergence was observed among European, Asian and South African population [ 46 ]. Another study of Abdelhedi et al, focused on the CYP2C9 and CYP2C19 variants implicated in the metabolism of anticoagulant response, concluded that Tunisians were similar to Europeans and Middle Easterners with regard to the allelic frequencies [ 27 ]. Pairwise Fst values of clinically relevant VIP variants, in our study, also revealed a more similarity between Tunisian, Tuscan and European populations (CEU).…”

Section: Discussionmentioning

confidence: 99%

“…These common polymorphisms were shown to confer a high risk towards over-anticoagulation, predisposing the individuals carrying these polymorphisms to hemorrhagic incidents [ 22 ]. In addition, a variable response to beta-blockers used in the treatment of hypertension, including propranolol [ 23 ], metoprolol, atenolol [ 24 ] and clopidogrel [ 25 , 26 ] was observed in patients of European and African origins which can trigger a stroke [ 27 , 28 ]. Other serious adverse outcomes of drugs in MetS are reported such as sudden death, bleeding events, myopathy, [ 2 , 20 , 27 , 29 ].…”

Section: Introductionmentioning

confidence: 99%

Pharmacogenetic landscape of Metabolic Syndrome components drug response in Tunisia and comparison with worldwide populations

et al. 2018

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Genetic variation is an important determinant affecting either drug response or susceptibility to adverse drug reactions. Several studies have highlighted the importance of ethnicity in influencing drug response variability that should be considered during drug development. Our objective is to characterize the genetic variability of some pharmacogenes involved in the response to drugs used for the treatment of Metabolic Syndrome (MetS) in Tunisia and to compare our results to the worldwide populations. A set of 135 Tunisians was genotyped using the Affymetrix Chip 6.0 genotyping array. Variants located in 24 Very Important Pharmacogenes (VIP) involved in MetS drug response were extracted from the genotyping data. Analysis of variant distribution in Tunisian population compared to 20 worldwide populations publicly available was performed using R software packages. Common variants between Tunisians and the 20 investigated populations were extracted from genotyping data. Multidimensional screening showed that Tunisian population is clustered with North African and European populations. The greatest divergence was observed with the African and Asian population. In addition, we performed Inter-ethnic comparison based on the genotype frequencies of five VIP biomarkers. The genotype frequencies of the biomarkers rs3846662, rs1045642, rs7294 and rs12255372 located respectively in HMGCR, ABCB1, VKORC1 and TCF7L2 are similar between Tunisian, Tuscan (TSI) and European (CEU). The genotype frequency of the variant rs776746 located in CYP3A5 gene is similar between Tunisian and African populations and different from CEU and TSI. The present study shows that the genetic make up of the Tunisian population is relatively complex in regard to pharmacogenes and reflects previous historical events. It is important to consider this ethnic difference in drug prescription in order to optimize drug response to avoid serious adverse drug reactions. Taking into account similarities with other neighboring populations, our study has an impact not only on the Tunisian population but also on North African population which are underrepresented in pharmacogenomic studies.

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“…Ethnicity significantly affects distributions of variants [ 124 ] and contributes to differences in MAF reported for populations outside of the MENA region for each of CYP2C9 [ 48 , 50 , 53 , 57 , 65 , 67 , 70 , 139 ], CYP2C19 [ 27 , 53 , 57 , 67 , 140 ], and MDR1 C3435T [ 132 , 141 , 142 ]. This emphasizes the importance of population-specific studies assessing genetic polymorphisms.…”

Section: Discussionmentioning

confidence: 99%

Impact of Genetic Polymorphisms on Phenytoin Pharmacokinetics and Clinical Outcomes in the Middle East and North Africa Region

et al. 2017

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BackgroundGenetic polymorphisms are known to influence outcomes with phenytoin yet effects in the Middle East and North Africa region are poorly understood.ObjectivesThe objective of this systematic review was to evaluate the impact of genetic polymorphisms on phenytoin pharmacokinetics and clinical outcomes in populations originating from the Middle East and North Africa region, and to characterize genotypic and allelic frequencies within the region for genetic polymorphisms assessed.MethodsMEDLINE (1946–3 May, 2017), EMBASE (1974–3 May, 2017), Pharmacogenomics Knowledge Base, and Public Health Genomics Knowledge Base online databases were searched. Studies were included if genotyping and analyses of phenytoin pharmacokinetics were performed in patients of the Middle East and North Africa region. Study quality was assessed using a National Institutes of Health assessment tool. A secondary search identified studies reporting genotypic and allelic frequencies of assessed genetic polymorphisms within the Middle East and North Africa region.ResultsFive studies met the inclusion criteria. CYP2C9, CYP2C19, and multidrug resistance protein 1 C3435T variants were evaluated. While CYP2C9*2 and *3 variants significantly reduced phenytoin metabolism, the impacts of CYP2C19*2 and *3 variants were unclear. The multidrug resistance protein 1 CC genotype was associated with drug-resistant epilepsy, but reported impacts on phenytoin pharmacokinetics were conflicting. Appreciable variability in minor allele frequencies existed both between and within countries of the Middle East and North Africa region.Conclusions CYP2C9 decrease-of-function alleles altered phenytoin pharmacokinetics in patients originating from the Middle East and North Africa region. The impacts of CYP2C19 and multidrug resistance protein 1 C3435T variants on phenytoin pharmacokinetic and clinical outcomes are unclear and require further investigation. Future research should focus on the clinical outcomes associated with phenytoin therapy.PROSPERO 2017: CRD42017057850

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Characterization of drug-metabolizing enzymes CYP2C9, CYP2C19 polymorphisms in Tunisian, Kuwaiti and Bahraini populations

Cited by 11 publications

References 19 publications

Detection of CYP2C19*2_ allele among Helicobacter pylori -infected patients in two tertiary hospitals of Khartoum, Sudan, 2019

Detection of CYP2C19*2_ allele among Helicobacter pylori -infected patients in two tertiary hospitals of Khartoum, Sudan, 2019

Pharmacogenetic landscape of Metabolic Syndrome components drug response in Tunisia and comparison with worldwide populations

Impact of Genetic Polymorphisms on Phenytoin Pharmacokinetics and Clinical Outcomes in the Middle East and North Africa Region

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