A PRELIMINARY STUDY ON CYTOCHROME 2E1 GENE SINGLE NUCLEOTIDE POLYMORPHISMS AMONG ETHNIC FULANI IN NORTH WESTERN NIGERIA

2021 ◽  
pp. 17-19
Author(s):  
Muhammad Tukur Umar ◽  
Shaibu Oricha Bello
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Consensus Sequence ◽  
Individual Variability ◽  
Nucleotide Position ◽  
Nucleotide Polymorphisms ◽  
Metabolizing Enzymes ◽  
Single Nucleotide ◽  
Cyp 2E1 ◽  
Preliminary Study ◽  
North Western

Single nucleotide polymorphisms of xenobiotics metabolizing enzymes are critical in inter-individual variability in drug response. Cytochrome P450 2E1, which is highly polymorphic belongs to these enzymes and ethnicity signicantly determine their expressions. Volunteers from Fulani extractions were recruited through their expressed consents. Five mls of blood sample was collected in EDTA container used for DNA extraction, PCR and sequencing. The consensus sequence generated for individual participants were located to the Cyp 2E1 gene and spanned both target rs 2031920 to rs 3813867 polymorphism region. Chromatograms were validated with Bioedit software. Three (3) volunteers (15%) revealed new rs 147346389 A>C polymorphism at nucleotide position 4029. Also, three (3) other volunteers (15%) revealed rs 35806299 A>G polymorphism at position 3661. One (5%) new (unlabelled) A>C polymorphism was revealed at position 3906.

A proposed HLA-B*27 screening method for ankylosing spondylitis detection based on tag-single nucleotide polymorphisms: a preliminary study

2021 ◽  
Author(s):  
Gabriela Angélica Martínez-Nava ◽  
Yessica Zamudio-Cuevas ◽  
Ninoska Aleida Terrazas-Ontiveros ◽  
Karina Martínez-Flores ◽  
Rolando Espinosa-Morales ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
Single Nucleotide Polymorphisms ◽  
Screening Method ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Preliminary Study

Influence of Genetic Single Nucleotide Polymorphisms in CYP3A4, CYP3A5, GSTP1, GSTM1, GSTT1 and MDR1 Genes on Survival and Treatment Related Toxicity in Patients with Multiple Myeloma Treated in the HOVON 24 Trial.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 505-505 ◽  
Author(s):  
Pieter Sonneveld ◽  
Celine Schilthuizen ◽  
Henk Lokhorst ◽  
Edo Vellenga ◽  
Reinier Raymakers ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Single Nucleotide Polymorphisms ◽  
Enzymatic Activity ◽  
Drug Metabolizing Enzymes ◽  
Nucleotide Polymorphisms ◽  
Metabolizing Enzymes ◽  
Single Nucleotide ◽  
Free Survival ◽  
Intensified Chemotherapy

Abstract Cytochromes P450 (CYP 450) and gluthatione-S-transferases (GSTs) are drug metabolizing enzymes involved in the detoxification of numerous chemotherapeutic agents.The Multidrug Resistance gene 1 (MDR1, ABCB1) is a transmembrane drug transporter present in tumor cells and mucosal epithelium. Genetic single nucleotide polymorphisms (SNP’s) in these genes are frequent and may alter the metabolism of certain anti-cancer drugs. The CYP3A4*1B (A-290G) polymorphism has not yet been proven to alter enzymatic activity. Polymorphisms in the CYP3A5*3 gene (A6986G) and the GSTP1 gene (Ile105Val) lead to decreased enzymatic activity. Homozygous deletions in the GSTM1 and GSTT1 genes lead to complete absence of the enzyme. Genetic polymorphism of MDR1 (C3435T) are frequent and associated with enhanced efflux function. We hypothesized that SNP haplotypes of these drug metabolizing enzymes may determine the interindividual differences of patients to treatment response and toxicity. We have investigated the presence of SNP’s of 211/345 previously untreated patients with multiple myeloma from whom diagnostic material was available and who were treated according to the HOVON-24 protocol, a clinical trial comparing myeloablative therapy with stem cell rescue added to intensified chemotherapy to intensified chemotherapy alone. Peripheral blood or bone marrow samples were analyzed by PCR or multiplex PCR. Patients with different haplotypes of CYP3A4, GSTP1, GSTM1, GSTT1 genes did not have significant differences of overall survival (OS), time to progression (TTP), progression free survival (PFS), event free survival (EFS), partial remission (PR), complete remission (CR) as determined by multivariate analysis with all clinical variables. Patients with mutant GSTP1(Ile/Val) had significantly more toxicity following high-dose melphalan (p=0.003). Patients with MDR1 C3435T mutation or absence of GSTP1 Ile105Val mutations had a lower probability to achieve at least a partial response(p=0.01). Patients genotyped homozygously for the mutant allele CYP3A5 gene had increased toxicity (p=0.040), improved OS (p=0.01) and PFS (p=0.04) and a decrease in TTP (p=0.03). This study is part of an ongoing analysis and the results will be validated in the next HOVON trial. We conclude that in patients with multiple myeloma who are treated with intensive chemotherapy and stem cell transplantation, analysis of genetic polymorphisms of metabolic enzymes may improve our understanding of treatment associated toxicity and treatment outcome.

scholarly journals Impact of CYP3A4 and CYP3A5 single nucleotide polymorphisms on anastrozole-associated adverse events among Malaysian breast cancer patients

2019 ◽  
pp. 33-42
Author(s):  
Murtala B. Abubakar ◽  
Huay Lin Tan ◽  
Venkata Murali Krishna Bhavaraju ◽  
Siew Hua Gan
Keyword(s):  
Breast Cancer ◽  
Single Nucleotide Polymorphisms ◽  
Adverse Events ◽  
Cancer Patients ◽  
Hot Flashes ◽  
Postmenopausal Breast Cancer ◽  
Individual Variability ◽  
Nucleotide Polymorphisms ◽  
Breast Cancer Patients ◽  
Single Nucleotide

The catalytic activity of the cytochrome P450A (CYP3A4) enzyme is reportedly affected by the presence of single nucleotide polymorphisms (SNPs), leading to inter-individual variability in drug efficacy and adverse reactions. CYP3A4 polymorphisms can serve as potential biomarkers for predicting the efficacy of many drugs, including those used in breast cancer treatment. This study was conducted on 94 hormone receptor-positive postmenopausal breast cancer patients who received 1 mg of anastrozole per day. Anastrozole-associated adverse events (AAAEs), such as musculoskeletal adverse events (MSAEs), hot flashes, mood disturbance and vaginal dryness/dyspareunia, were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE). The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was performed to determine the allelic frequency of CYP3A4*4, CYP3A4*18A, CYP3A4*18B, CYP3A4*22 and CYP3A5*3. The frequencies of CYP3A4*18A T>C (rs28371759), CYP3A4*18B G>A (rs2242480) and CYP3A5*3 were 0.03, 0.48 and 0.64, respectively. However, no CYP3A4*4 A>G (rs55951658) or CYP3A4*22 C>T (rs35599367) alleles were detected. No significant association was observed between the alleles and the development of AAAEs. We have demonstrated for the first time that CYP3A4*18B G>A is highly prevalent among Malaysian breast cancer patients. The clinical relevance of CYP3A4*18B is currently under investigation by our group.

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