Frequency of MDR1 single nucleotide polymorphisms in a Jordanian population, including a novel variant

Khabour, OF; Alzoubi, Karem H.; Si, Al-Azzam; Nm, Mhaidat

doi:10.4238/2013.march.13.9

Cited by 6 publications

(2 citation statements)

References 36 publications

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“…The distribution of G2677T/A and C1236T SNPs also shows variation among populations with high frequency of the mutant alleles among Africans and Asians (Cascorbi 2011;Gaikovitch et al 2003;Milojkovic et al 2011). We have recently reported that the MDR1 variants distribution among Jordanians is similar to that of Caucasians (Khabour et al 2012). …”

Section: Discussionmentioning

confidence: 88%

The role of Multidrug Resistance-1 (MDR1) variants in response to atorvastatin among Jordanians

et al. 2014

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The MDR1 gene encodes for P-glycoprotein (P-gp), which is an efflux transporter at the cell membrane. The P-gp has wide substrate specificity for multiple medications including the lipid lowering drug, atorvastatin. In this study, we investigated the possible association between three common MDR1 gene polymorphisms (G2677T, C3435T, and C1236T), and the lipid lowering effect of atorvastatin among Jordanians. Lipid and lipoproteins were measured in blood samples collected from patients (n = 201) at baseline and during atorvastatin treatment. MDR1 polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism. Both the TT genotype of G2677T and the TT genotype of the C3435T polymorphisms were associated with lower levels of low-density lipoproteins after atorvastatin treatment. However, the effects of atorvastatin on the levels of total cholesterol, triglycerides, and high-density lipoprotein, were not correlated with any of the genotypes in both polymorphisms. Finally, the C1236T polymorphism was not associated with the lipid lowering effect of atorvastatin. In conclusion, the MDR1 gene polymorphisms G2677T, and C3435T, but not C1236T were associated with the lipid lowering effect of atorvastatin among Jordanians.

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Section: Discussionmentioning

confidence: 88%

The role of Multidrug Resistance-1 (MDR1) variants in response to atorvastatin among Jordanians

et al. 2014

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“…ABCB1 is involved in diseases and the efficacy of therapy, where SNPs in the ABCB1 gene affect its function. Polymorphisms of ABCB1 rs1128503 and rs1045642 are the most studied variants genetic of ABCB1 in diseases and indicate high frequencies in several populations [ 45 , 46 ]. This was the first genotype variation study of ABCB1 in Indonesian TB patients, especially in the Jambi population, although we did not find a significant association with sociodemography characteristics or duration of therapy.…”

Section: Main Textmentioning

confidence: 99%

Genetic variation of ABCB1 (rs1128503, rs1045642) and CYP2E1 rs3813867 with the duration of tuberculosis therapy: a pilot study among tuberculosis patients in Indonesia

et al. 2021

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Objective The risk of contracting tuberculosis (TB) and the efficacy of TB therapy are affected by several factors, including genetic variation among populations. In the Indonesian population, data on the genes involved in drug transport and metabolism of TB therapy are limited. The aim of this study was to identify the genetic profile of the ABCB1 gene (rs1128503 and rs1045642) and CYP2E1 gene (rs3813867) in Indonesians with TB. This study was a cross-sectional study of 50 TB outpatients in Jambi city, Indonesia. Sociodemographic characteristics were obtained from medical records. Whole blood was collected, and genomic DNA was isolated. Single nucleotide polymorphisms were determined using polymerase chain reaction-restriction fragment length polymorphism with HaeIII, MboI, and PstI for rs1128503, rs1045642 (ABCB1), and rs3813867 (CYP2E1), respectively. Result The frequency of alleles of each gene was analyzed by Hardy–Weinberg equilibrium. The genetic profiles of ABCB1 rs1128503 and rs1045642 were varied (CC, CT, TT), while CYP2E1 rs3813867 was present in CC (wild type). The genetic variations of ABCB1 and CYP2E1 may have no significant correlation with the duration of TB therapy. Nevertheless, this study may provide as preliminary results for the genetic profiles of ABCB1 (rs1128503, rs1045642) and CYP2E1 (rs3813867) in the Indonesia population.

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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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Frequency of MDR1 single nucleotide polymorphisms in a Jordanian population, including a novel variant

Cited by 6 publications

References 36 publications

The role of Multidrug Resistance-1 (MDR1) variants in response to atorvastatin among Jordanians

The role of Multidrug Resistance-1 (MDR1) variants in response to atorvastatin among Jordanians

Genetic variation of ABCB1 (rs1128503, rs1045642) and CYP2E1 rs3813867 with the duration of tuberculosis therapy: a pilot study among tuberculosis patients in Indonesia

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

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