Genetic Polymorphism of Cytochrome p450 (2C9) Enzyme in Iranian Baluch Ethnic Group

Tabari, Mojdeh Ghiyas; Naseri, Fatemeh; Ataby, Maryam Agh; Marjani, Abdoljalal

doi:10.2174/1874091x01509010037

Cited by 6 publications

(11 citation statements)

References 26 publications

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“…1 . Of the 30 articles screened for eligibility, ten were excluded for subjects not originating from the MENA region [ 17 – 26 ], seven were excluded for phenytoin concentrations not being assessed [ 27 – 33 ], five were excluded for both subjects not originating from the MENA region and phenytoin concentrations not being assessed [ 34 – 38 ], one was excluded for genetic polymorphisms not being assessed [ 39 ], and two were excluded for being poster abstracts [ 40 , 41 ]. Between the five included studies , CYP2C9*1, *2, and *3; CYP2C19*1, *2, and *3; and multidrug resistance protein 1 [ MDR1 , also known as ATP-binding cassette sub-family B member 1 (ABCB1)] C3435T polymorphisms were evaluated.…”

Section: Resultsmentioning

confidence: 99%

“…A total of 82 studies were conducted within the MENA region and investigated the prevalence of CYP2C9 , CYP2C19 , and/or MDR1 variant alleles [ 27 , 29 , 42 – 121 ]. These studies were included in the secondary part of the review.…”

Section: Resultsmentioning

confidence: 99%

“…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%

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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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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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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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“…[ 22 24 ] With regard to ethnic diversity in Iran, epidemiological studies have been conducted to determine the distribution of CYP2C19 allele variants in different ethnic groups. [ 25 26 27 ] A recent study by Payan et al . revealed that 21.7% of Iranian population were carriers of CYP2C19*17 and 34.4% of studied population exhibited CYP2C19*1*17 and CYP2C19*17*17 genotypes.…”

Section: Discussionmentioning

confidence: 99%

Impact of CYP2C19 polymorphisms on serum concentration of voriconazole in iranian hematological patients

et al. 2017

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Objective:This study aimed to determine the portion of Iranian patients who attain therapeutic serum concentrations of voriconazole (VRCZ) following administration of fixed doses. In addition, the effect of CYP2C19 polymorphism on serum levels of VRCZ was also investigated.Methods:Forty-eight adult patients of Iranian origin with hematologic malignancies, who received VRCZ for treatment of invasive aspergillosis, were recruited into the study. Blood samples were drawn at day 4 of treatment to measure trough drug concentrations and determine genotyping of CYP2C19 polymorphisms of each patient. High-performance liquid chromatography method was used for measuring VRCZ serum level and CYP2C19 polymorphisms were conducted by Sanger sequencing. Demographic and clinical characteristics of patients alongside with CYP2C19 polymorphisms were assessed to determine the effective factor/s on VRCZ serum concentration.Findings:Seventy-three percent of patients achieved therapeutic serum concentrations of VRCZ with administration of usual fixed doses in clinical practice. There was no correlation between weight-adjusted dose and serum concentrations of VRCZ. Mean serum levels were significantly different neither in genders nor in routes of administrations. Extensive and ultrarapid metabolizers (URMs) comprised 48.7% and 21.6% study population, respectively. CYP2C19 polymorphism dramatically influenced the trough levels of VRCZ, so that all patients with subtherapeutic levels expressed URM phenotype.Conclusion:With respect to high incidence of URM phenotype in Iranian population, and observed association of this phenotype with sub-therapeutic levels in our study, performing therapeutic drug monitoring is strongly recommended for all patients.

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“…As mentioned earlier, these alleles may change the catalytic activity of CYP2C9 [6] and on the other hand, many studies have shown the variations among different ethnic groups. We have previously studied the genetic polymorphism of CYP2C9 gene among different ethnic groups in Golestan province [14,15]. This study aimed to assess the distribution of CYP2C9 allele and its genotypic variants in Sistani ethnic group in the city of Gorgan, South East of Caspian Sea, and North East of Iran.…”

Section: Introductionmentioning

confidence: 99%

Genetic Polymorphism of CYP2C9 Among Sistani Ethnic Group in Gorgan

Marjani

Gharanjik

2017

Ind J Clin Biochem

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Cytochrome P450 2C9 (CYP2C9) is involved in metabolism of many important drugs and its genotype variations is thought to affect drug efficacy and the treatment process. The aim of this study was to assess the distribution of CYP2C9 allele and genotypic variants in Sistani ethnic group, living in Gorgan, South East of Caspian Sea and North East of Iran. This study included 140 Sistani, referred to the health center of Gorgan. CYP2C9 genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism technique. The allele frequency of CYP2C9*1, CYP2C9*2 and CYP2C9*3 was 76.1, 16.1 and 7.8%, respectively. The frequency of CYP2C9*1/*1, CYP2C9*1/*2, CYP2C9*1/*3, CYP2C9*2/*2, CYP2C9*2/*3 and CYP2C9*3/*3 genotypes was 53.9, 22.1, 11.4, 2.9, 4.3% and nil, respectively. In this study the genotypic variations of the CYP2C9 allele among the Sistani ethnic group was investigated and great differences were observed in comparison to other populations. Our findings suggest that different genotypes of may influence the pharmacokinetics of some drugs. More studies on the pharmacokinetic effects of genotypes may help physicians choose optimal dosage of some drugs for treatment and prevention of their side effects. Since different ethnic groups from all over the world use medications, it suggests to investigate the pharmacokinetic effects of genotypes in different populations.

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Genetic Polymorphism of Cytochrome p450 (2C9) Enzyme in Iranian Baluch Ethnic Group

Cited by 6 publications

References 26 publications

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

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

Impact of CYP2C19 polymorphisms on serum concentration of voriconazole in iranian hematological patients

Genetic Polymorphism of CYP2C9 Among Sistani Ethnic Group in Gorgan

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