Frequencies of ThreeCYP2D6Nonfunctional Alleles (CYP2D6*3,*4, and*6) Within an Iranian Population (Mazandaran)

Hashemi‐Soteh, Mohammad Bagher; Sarzare, Fatemeh; Merat, Fatemeh; Salehifar, Ebrahim; Shiran, Mohammad-Reza

doi:10.1089/gtmb.2011.0033

Cited by 12 publications

(13 citation statements)

References 36 publications

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“…A limitation of our study is the number of patients included. Previous studies have shown a low frequency of CYP2D6 PM subjects in the Iranian population (Kouhi et al, 2009; Hashemi-Soteh et al, 2011; Bagheri et al, 2015). In line with these findings, the number of PM patients was not high enough to analyze those patients separately.…”

Section: Discussionmentioning

confidence: 89%

“…Regarding the Iranian population and the ethnic background few studies indicate the most relevant CYP2D6 alleles (Kouhi et al, 2009; Hashemi-Soteh et al, 2011; Bagheri et al, 2015). Accordingly, we decided to genotype the breast cancer patients of our study for the CYP2D6 alleles ∗ 1, ∗ 2, ∗ 4, ∗ 5, ∗ 6, ∗ 10, ∗ 17 , and ∗ 41 as well as the gene duplication to comprehensively cover CYP2D6 alleles representative of the Iran population (Isfahan province).…”

Section: Introductionmentioning

confidence: 99%

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Clinical Trial: CYP2D6 Related Dose Escalation of Tamoxifen in Breast Cancer Patients With Iranian Ethnic Background Resulted in Increased Concentrations of Tamoxifen and Its Metabolites

et al. 2019

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Introduction: The polymorphic enzyme cytochrome P450 2D6 (CYP2D6) catalyzes a major step in the bioactivation of tamoxifen. Genotyping of clinically relevant CYP2D6 alleles and subsequent dose adjustment is a promising approach to individualize breast cancer therapy. The aim of this study was to investigate the relationship between the plasma levels of tamoxifen and its metabolites and different CYP2D6 genotypes under standard (20 mg/day) and dose-adjusted therapy (Registration ID in Iranian Registry of Clinical Trials: IRCT2015082323734N1). Materials and Methods: Using TaqMan ® assays common alleles of CYP2D6 ( ∗ 1, ∗ 2, ∗ 4, ∗ 5, ∗ 6, ∗ 10, ∗ 17, and ∗ 41) and gene duplication were identified in 134 breast cancer patients. Based on CYP2D6 genotypes patients with an activity score 1 ( n = 15) and 0–0.5 ( n = 2) were treated with tamoxifen adjusted dosage of 30 and 40 mg/day, respectively. The concentration of tamoxifen and its metabolites before and after 4 and 8 months of dose adjustment were measured using LC-MS/MS technology. Results: At baseline, (Z)-endoxifen plasma concentrations (33 ± 15.5, 28.1 ± 14, 26.6 ± 23.4, 14.3 ± 8.6, and 10.7 ± 5.5 nmol/l for EM/EM, EM/IM, EM/PM, IM/IM and PM/PM, respectively) and the metabolic ratio (Z)-Endoxifen/N-desmethyltamoxifen (0.0558 ± 0.02, 0.0396 ± 0.0111, 0.0332 ± 0.0222, 0.0149 ± 0.0026, and 0.0169 ± 0.0177 for EM/EM, EM/IM, EM/PM, IM/IM, and PM/PM, respectively) correlated with CYP2D6 genotype (Kruskal–Wallis p = 0.013 and p < 0.0001, respectively). Dose escalation to 30 and 40 mg/day in patients with a CYP2D6 activity score of 1 ( n = 15) and 0–0.5 ( n = 2) resulted in a significant increase in (Z)-endoxifen plasma levels (22.17 ± 24.42, 34.43 ± 26.54, and 35.77 ± 28.89 nmol/l at baseline, after 4 and 8 months, respectively, Friedman p = 0.0388) along with the plasma concentrations of tamoxifen and its other metabolites. No severe side effects were recorded during dose escalation. Conclusion: For the first time, we show the feasibility of dose escalation of tamoxifen in breast cancer patients with compromised CYP2D6 activity and Iranian ethnic background to increase the plasma concentrations of (Z)-endoxifen.

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Section: Discussionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Clinical Trial: CYP2D6 Related Dose Escalation of Tamoxifen in Breast Cancer Patients With Iranian Ethnic Background Resulted in Increased Concentrations of Tamoxifen and Its Metabolites

et al. 2019

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“…A total of 5 mL of peripheral blood was collected in EDTA from each person, and genomic DNA was extracted according to established protocols . The GAP‐PCR protocol, described by Baysal and Huisman, was primarily applied for all samples to detect α3.7 (3.7 kb), α4.2 (4.2 kb), ‐‐MED, ‐‐20.5, and ‐‐SEA variations, as a primary screening test .…”

Section: Methodsmentioning

confidence: 99%

Alpha‐globin gene mutation spectrum in patients with microcytic hypochromic anemia from Mazandaran Province, Iran

Hashemi‐Soteh

Karami

Mousavi³

et al. 2019

Clinical Laboratory Analysis

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Background:It is estimated about 7% of the world population is carriers of hemoglobin diseases. Alpha-thalassemia is one of the most common hereditary hemoglobin disorders in the world. This study investigated alpha-globin mutations in potential carriers with hypochromic and microcytic anemia from Mazandaran, in northern Iran. Methods:A total of 859 subjects were selected; genomic DNA was extracted and examined for the presence of mutations in the alpha-globin genes.Results: Mutation analysis of alpha-globin genes revealed 27 different mutations.Seven variants were seen in 91.45% of all alpha-1 and alpha-2 mutations among patients in this study. The 3.7 kb deletion is the most frequent mutation with a frequency of 49.53%, followed by PolyA2 (15.19%), −4.2 deletion (8.76%), --MED (5.84%), IVSI-5nt deletion (5.49%), Hb constant spring (3.62%), and Cd 19 (−G; 3.04%), respectively. There are also seven new variants which were reported for the first time either in alpha-1 or alpha-2 genes, including codon 9 (C > A; α2), deletion of codon 60 (AAG deletion; α2), duplication of codon 94-100 plus 3 base pairs of intron 2 (IVSII + 3; α1), codon 99 (C > A; α2), codon 108 (A > G; α2), codon 128 (A > T; α2), and codon 129 (T > G; α2), respectively. The MLPA method also revealed three rare and novel deletions in alpha-cluster region with about 30 kilobases long. Conclusion:This study showed an efficient identification of α-thalassemia can be achieved using standard hematological indices in our population. The details of these variations will help local genetic services for diagnostic and prenatal diagnosis services. K E Y W O R D S alpha-thalassemia, Iran, Mazandaran, mutation, thalassemiaThis is an open access article under the terms of the Creat ive Commo ns Attri butio n-NonCo mmercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

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“…The samples were then subjected to a final extension step at 72 °C for 5 min. A 6-μl aliquot of each PCR product was run on a 1% flatbed agarose gel to check for positive amplification [ 6 , 18 ].…”

Section: Methodsmentioning

confidence: 99%

Haplotypes inside the beta-globin gene: use as new biomarkers for beta-thalassemia prenatal diagnosis in north of Iran

Hashemi‐Soteh

Mousavi²,

Tafazoli

2017

J Biomed Sci

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BackgroundBeta-thalassemia is common in the Mediterranean area as well as the Middle East and India. Official report in Iran revealed the average prevalence rate of carriers about 4%. More than 20 restriction fragment length polymorphisms (RFLPs) are known in the beta-globin gene cluster and used in the prenatal diagnosis (PND) services. Some of these locations may have low allele frequency and are not informative in the prenatal diagnosis. The current study aims to find new haplotypes and polymorphisms with high allele frequency in the local population.MethodsTwo thousand three hundred fifty samples (1,321 male and 1,029 female) from the northern Iran, whom suspected to be the carriers either for alpha or beta thalassemia and referred to the local diagnostic laboratory as a routine services were investigated during five years, (2010–2015). The beta-globin gene was sequenced for all samples.ResultsHeterozygosity for five SNPs in the beta-globin gene was calculated separately. 383 individuals (16.29%) showed no sign of nucleotide change in the beta-globin gene sequence. In total, codon2 (C/T) 31.72%, IVSII-16 (C/G) 31.72%, IVSII-74 (G/T) 54.71%, IVSII-81 (C/T) 19.47%, and IVSII-666 (T/C) 31.72% were seen respectively. Although all five polymorphisms showed reasonably high heterozygosity, IVSII-74 (G/T) [GG wild type (36.5%), G/T (54.71%) and TT (8.8%)] revealed the highest heterozygosity rate. Four combinations of these five SNPs were defined as new haplotypes named M1 to M4. ARMS-PCR also were designed and applied to detect IVSII-74 (G/T) nucleotide position.ConclusionsThis study represents an intragenic polymorphism, IVSII-74, a reliable position with high heterozygosity rates in Iranian population for PND analysis.Trial registrationRetrospectively registered.

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Frequencies of ThreeCYP2D6Nonfunctional Alleles (CYP2D63*,4, and6) Within an Iranian Population (Mazandaran)

Cited by 12 publications

References 36 publications

Clinical Trial: CYP2D6 Related Dose Escalation of Tamoxifen in Breast Cancer Patients With Iranian Ethnic Background Resulted in Increased Concentrations of Tamoxifen and Its Metabolites

Clinical Trial: CYP2D6 Related Dose Escalation of Tamoxifen in Breast Cancer Patients With Iranian Ethnic Background Resulted in Increased Concentrations of Tamoxifen and Its Metabolites

Alpha‐globin gene mutation spectrum in patients with microcytic hypochromic anemia from Mazandaran Province, Iran

Haplotypes inside the beta-globin gene: use as new biomarkers for beta-thalassemia prenatal diagnosis in north of Iran

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