The allele frequencies for eight short tandem repeat (STR) loci HUMvWA, HUMFES/FPS, HUMF13A, HUMF... more The allele frequencies for eight short tandem repeat (STR) loci HUMvWA, HUMFES/FPS, HUMF13A, HUMF13B, HUMTHO1, HUMTPOX, HUMCSF1P0, HUMLPL included in Geneprint TM STR kits were obtained from 234 unrelated individuals in Casablanca. #
This article presents a literature review, which aims to establish a link between the success of ... more This article presents a literature review, which aims to establish a link between the success of pulp revascularization as a new therapeutic approach of teeth with necrotic pulp, and the state of pregnancy in women. The success of pulpal revascularization depends essentially on the availability of stem cells and the presence of growth factors that will direct the differentiation of these cells to a specific cell line. An electronic search was conducted on PUBMED, Cochrane, and Journal of Endodontics using the following keywords: pulp revascularization, pregnancy, growth factors, dental pulp stem cells, . Then, and in order to identify items that would have escaped the electronic search, a manual search was performed from the list of pre-selected items.
Pulpal capping, as it has been used for more than 200 years, helps to preserve the vital pulp and... more Pulpal capping, as it has been used for more than 200 years, helps to preserve the vital pulp and the dentinogenic potential of the tooth. Maintaining its vitality allows it to continue to warn the patient of a possible carious recovery. First made with different materials, it was a resounding success. The evolution of materials, techniques and knowledge of the dentin-pulp complex has gradually improved its results. Nowadays, there are many direct and indirect pulp capping materials. Some, present for more than 50 years, like calcium hydroxide or ZOE, have proven their worth. Others, such as Biodentine or MTA, which are very recent, show promising results. The aim of this paper is to accomplish a literature review concerning this issue.
Background: Antiplatelet drugs are recommended as one of the main medications used in Acute Coron... more Background: Antiplatelet drugs are recommended as one of the main medications used in Acute Coronary Syndromes (ACS) patients. However, an inter-individual variability in platelet response to Clopidogrel has been found in a substantial group of them. Genetic is known be the dominant influencing factor for individual and interethnic variations in drug responses. Polymorphisms in the genes involved in Clopidogrel absorption, biotransformation to the active metabolite, or platelet response to adenosine diphosphate (ADP) have been associated to this impaired response. Interestingly, Multi-Drug Resistance gene-1 (MDR-1) polymorphism influences oral bioavailability of clopidogrel and prognosis of ACS patients. The objectives of our study are, first, to determine the frequency of the C3435T MDR1 polymorphism among Moroccan ACS patients compared to healthy subjects; and second, to assess its effect on Clopidogrel response in a sample of Moroccan ASC patients. Methods and results: 40 ACS pat...
Effect of Allium sativum extract on human PBMC proliferation. CD4 T cell division was evaluated b... more Effect of Allium sativum extract on human PBMC proliferation. CD4 T cell division was evaluated by CFSE staining and flow cytometry when PBMCs were treated with or without A.S. at two different doses in the absence or presence of PHA (a) or Okt-3 mAb (b). CD8 T cell division assessed by CFSE staining and flux cytometry within PBMCs treated with or without A.S. at two doses in the absence or presence of PHA (c) or Okt-3 mAb (d). Data shown are representative of 4 independent experiments. Percentage of cell division was calculated with FlowJo software. Data are represented in mean ± S.D. and were analyzed using the one-way ANOVA test. (DOCX 278 kb)
Background: According to numerous studies, FMS-like tyrosine kinase 3, internal tandem duplicatio... more Background: According to numerous studies, FMS-like tyrosine kinase 3, internal tandem duplication, and the D835 mutation are associated with a poor prognostic clinical outcome in acute myeloid leukemia patients. Detection of the FMS-like tyrosine kinase 3 mutation in patients who present with normal karyotype acute myeloid leukemia helps in both the understanding of the disease and the treatment of patients. This study evaluates the incidence of FMS-like tyrosine kinase 3-internal tandem duplication and FMS-like tyrosine kinase 3-D835 mutation in newly diagnosed patients with normal karyotype acute myeloid leukemia. Methods: This study looked at 33 new cases who presented with normal karyotype acute myeloid leukemia at diagnosis. We collected peripheral blood samples from patients at diagnosis. FMS-like tyrosine kinase 3-internal tandem duplication mutation was detected using polymerase chain reaction and FMS-like tyrosine kinase 3-D835 mutation by restriction fragment length polym...
Breast cancer is the most common cancer affecting women all over the world. In addition to hormon... more Breast cancer is the most common cancer affecting women all over the world. In addition to hormonal and environmental causes, family history is emerging as an important risk factor in the etiology of this disease. The aim of the present study is thus to compare the clinico-pathological features of familial and sporadic breast cancer in Moroccan patients. A comparative retrospective cohort study was conducted on 570 women with familial and sporadic breast cancer who were diagnosed and treated in the Oncology Center of Ibn Rochd University Hospital in 2009. Data on breast cancer risk factors and clinico-pathological characteristics of the tumors were extracted from patients' medical records. Familial cases represented 18.4% of breast cancer patients. The age of onset appears to be earlier in familial breast cancers (P=0.0024). There were no significant differences between familial and sporadic groups according to histological type, tumor size and estrogen receptor status. However,...
Nowadays, many genes are associated with Breast Cancer. In order to understand the cause behind t... more Nowadays, many genes are associated with Breast Cancer. In order to understand the cause behind this particular type of cancer, we chose to study crucial genes previously reported to be involved in its development and mechanisms. Therefore, we worked on BRCA1 and BRCA2 as the main predisposition genes related to 5 to 10% of familial cases and assessed TP53 since it's associated to > 50% types of cancer. Additionally, we measured MDM2 , BAX and CASP3 giving their important role in the internal pathway of apoptosis. For a molecular characterization, we quantified BRCA1 , BRCA2 , TP53 , MDM2 , BAX and CASP-3 mRNA using the qRT-PCR approach in large series of tumor and normal breast tissues of Moroccan patients. We found a significant correlation between the expression of BRCA1 and BRCA2 in normal and tumor tissue. The results showed a positive correlation in the expression of MDM2 between normal and tumor tissue. Furthermore, we detected an elevation of expression of CASP-3 and ...
Acute myeloid leukemia (AML) is a very complex disease that is linked to environmental, genetic a... more Acute myeloid leukemia (AML) is a very complex disease that is linked to environmental, genetic and epigenetic factors. Several Studies have found that aberrations in DNA methylation process play a crucial role in leukemogenesis. The aim of this case control study was to evaluate the association between rs1569686, rs2424913 polymorphisms located in DNMT3B gene and rs7590760 polymorphism located in DNMT3A gene and AML risk in a Moroccan population. MATERIALS AND METHODS The present study was conducted in 142 cases of AML and 179 control subjects from the Moroccan population. Genomic DNA was isolated from whole blood samples by salting-out method and the genotype of the three polymorphisms was determined by the PCR-RFLP technique. RESULTS The study results indicated that rs1569686 polymorphism was significantly associated with the risk of AML in dominant model (OR=1.72, 95 % CI 1.01-2.95, P=0.04), but not in recessive model. In stratified analysis by gender, statistically significant association between the rs2424913 CT genotype and AML was found among males (OR=2.05, 95 % CI 1.00-4.19, P=0.04). Similarly, the rs1569686 TT genotype was associated with an increase risk of AML (OR=3.21, 95 % CI 1.15-8. 98, P=0.02), this association was also found under dominant genetic model (OR=2.47, 95 % CI 1.07-5. 67, P=0.03) among males. However, the rs2424913 polymorphism was not associated with AML. CONCLUSION Our findings have shown that rs1569686 polymorphism might be a risk factor of AML in males. While, the rs2424913 polymorphism was not associated with AML. Further studies with a large sample size are needed to validate our results.
Background: Acute myeloid leukemia (AML) is a complex disease that is linked to genetic and envir... more Background: Acute myeloid leukemia (AML) is a complex disease that is linked to genetic and environmental factors. The gluthatione S-transferase (GST) is a family of enzymes that play a crucial role in the detoxification of carcinogens. These compounds could cause DNA damage, which might lead to the development of cancer. Interindividual inherited differences caused by the presence of single nucleotide polymorphisms (SNPs) in detoxification enzyme, could play a major role in cancer predisposition. The present study aimed to investigate the association between GST gene polymorphisms and AML risk. Methods: The GSTP1 genotype was determined by the PCR-RFLP and multiplex PCR for GSTT1 and GSTM1. Meta-analysis was conducted to evaluate the association between GST gene and the risk of AML. Results: We found that GSTT1 null genotype was significantly associated with the risk of AML. However, GSTM1 and GSTP1 polymorphisms did not influence the AML risk. Subjects carrying the GSTM1 Present, ...
Abstract Cytochrome P450 enzymes play a central role in the phase I biotransformation process of ... more Abstract Cytochrome P450 enzymes play a central role in the phase I biotransformation process of a wide range of compounds, including xenobiotics, drugs, hormones and vitamins. It is noteworthy that these enzymes are highly polymorphic and, depending on the genetic makeup, an individual may have impaired enzymatic activity. Therefore, the identification of genetic variants in these genes could facilitate the implementation of pharmacogenetic studies and genetic predisposition to multifactorial diseases. We have established the frequencies of CYP2B6 (rs3745274; rs2279343) and CYP3A4 (rs2740574) alleles and genotypes in 209 healthy Malian subjects using TaqMan drug metabolism genotyping assays for allelic discrimination. Allele frequencies were 37% for CYP2B6 rs3745274; 38% for CYP2B6 rs2279343; and 75% for CYP3A4 rs2740574 respectively. Overall, the frequencies observed in Mali are statistically comparable to those reported across Africa except North Africa. The major haplotypes in CYP2B6 rs3745274 and CYP2B6 rs2279343 were represented by GA (60.24%) followed by TG (35.36%). We noted a strong linkage disequilibrium between CYP2B6 rs3745274 and CYP2B6 rs2279343 with D’ = 0.91 and r2 = 0.9. The frequencies of the genotypic combinations were 43.5% (GT/AG), 37.3% (GG/AA) and 11.5% (TT/GG) in the combination of CYP2B6-rs3745274 and CYP2B6-rs2279343; 26.8% (GT/CC), 25.4%, (GT/CT), 17.2% and GG/CT in the combination CYP2B6-rs3745274-CYP3A4-rs2740574; 26.8% (AG/CC), 23.9% (AA/CC), 19.1% (AG/CT), and 11% (AA/CT) in the combination CYP2B6-rs2279343-CYP3A4-rs2740574, respectively. The most common triple genotype was GT/AG/CC with 24.9%, followed by GG/AA/CC with 23.9%, GT/AG/CT with 16.7%, and GG/AA/CT with 10%. Our results provide new insights into the distribution of these pharmacogenetically relevant genes in the Malian population. Moreover, these data will be useful for studies of individual genetic variability to drugs and genetic predisposition to diseases.
Abstract Background as it is the case for all kinds of cancer; lung cancer is a multifactorial di... more Abstract Background as it is the case for all kinds of cancer; lung cancer is a multifactorial disease. The interaction between both Exposures to different carcinogens and individual genetic backgrounds modulate the disease risk. Cytochrome P450 family is one of the main enzymes involved in the metabolism of these carcinogens. Therefore, polymorphisms of genes encoding for the cyp450 enzymes can be responsible for the inter-individual differences in lung cancer susceptibility. In this study, we chose to focus on the Cyp2c19, as one of the crucial cyp450 enzymes associated with metabolism of a number of drugs and xenobiotics and its association with the lung cancer risk. Methods peripheral blood from a total of 115 Moroccan patients diagnosed with lung cancer and 105 healthy subjects was collected. The genotyping of CYP2C19*2 and CYP2C19*3 polymorphisms was carried out using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technic. Results we found that the frequency of both CYP2C19*2 (GA+AA) genotype and CYP2C19*A allele were significantly more frequent in lung cancer patients than that in control subjects (24.3% vs 13.3%; p=0.04 and 14.35% vs 7.15%; p=0.01 respectively). We also found that the CYP2C19*3 A allele was only found in lung cancer patient with a frequency of 10% (p= 0.007). Consequently, the frequency of the CYP2C19*3 (GA+AA) genotype was also significantly more prevalent in lung cancer patients than that in controls (20% vs 0.00%; p=0.005). We also found that smoking is associated to a higher lung cancer risk in participants carrying CYP2C19*3 or CYP2C19*2 GG genotypes (p Conclusion These findings indicate that the CYP2C19*2 and CYP2C19*3 polymorphisms are significantly associated with lung cancer in Moroccan population. In addition, that the coexistence of CYP2C19*3 with smoking increased lung cancer risk even more.
Abstract Background Low-Grade Gliomas are the most common brain tumor in children. They are chara... more Abstract Background Low-Grade Gliomas are the most common brain tumor in children. They are characterized by a broad spectrum of very heterogeneous tumor subtypes. Their current definition is mainly based on histological criteria which represents an important limit because these classifications suffer from a lack of precision. Recent advances in genomics allow us to considerably deepen our knowledge of the biology of these tumors in order to enrich their current classification. Aim In this work, we studied the frequency of KIAA1549/BRAF fusion in 89 pLGG tissues of Moroccan patients with Pediatric Low-Grade Gliomas, using PCR-RFLP and Fluorescence In Situ Hybridization and we compared our results with the frequency of KIAA1549/BRAF fusion in 123 pHGG tissues of Moroccan patients with Pediatric High-Grade Gliomas. Methodology We studied the frequency of KIAA1549/BRAF fusion in 89 pLGG tissues, using PCR-RFLP and Fluorescence In Situ Hybridization. Data was analyzed by using IBM SPSS software v24. Results 32 patients with pLGG had a positive KIAA1549/BRAF fusion, compared to 57 with a negative KIAA1549/BRAF fusion by using PCR-RFLP and Fluorescence In Situ Hybridization. Based on our findings, the frequency of KIAA1549/BRAF fusion in Moroccan patients with Pediatric Low-Grade Gliomas is 36.0% in the pLGGs and there is significant relationship between the presence of KIAA1549/BRAF fusion in pLGGs and pHGGs (P Conclusion We hope that the results of this study will contribute to the improvement of the molecular and histopathological classification of Pediatric Low-Grade Gliomas (pLGGs) and bring innovations to patient treatment by establishing new clinical trials and experimental studies, as well as a more precise categorization for epidemiological purposes.
Triple-negative breast cancer (TNBC) can be distinguished from other breast malignancies by the l... more Triple-negative breast cancer (TNBC) can be distinguished from other breast malignancies by the lack of expression of estrogen receptors (ER), progesterone receptors (PR) as well as human epidermal growth factor receptor 2 (HER2). TNBC is associated with adverse clinical outcomes and high risk of metastasis. Currently, several clinical and translational reports are focusing on developing targeted therapies for this aggressive cancer. In addition to approved targeted drugs such as poly(ADP-ribose) polymerase inhibitors (PARPi) and immune-checkpoint inhibitors, platinum-based chemotherapy is still a cornerstone therapeutic option in TNBC. However, despite the observed improved outcomes with platinum- based chemotherapy in TNBC, there is still a large proportion of patients who do not respond to this treatment, hence, the need for predictive biomarkers to stratify TNBC patients and therefore, avoiding unwanted toxicities of these agents. With the emergence of genetic testing, several r...
Background Breast cancer, the most common tumor in women in Mali and worldwide has been linked to... more Background Breast cancer, the most common tumor in women in Mali and worldwide has been linked to several risk factors including genetic factors, such as the PIN3 16-bp duplication polymorphism of TP53 gene. The aim of our study was to evaluate the role of the PIN3 16-bp duplication polymorphism in the susceptibility to breast cancer in the Malian population and to perform a meta-analysis to better understand the correlation with data from other populations.Methods We analyzed the PIN3 16-bp duplication polymorphism in blood samples of 60 Malian women with breast cancer and 60 healthy appearing Malian women using PCR. In addition, we performed a meta-analysis of data from case-control studies published in articles retrieved from international databases (Pubmed, Harvard University Library, Genetics Medical Literature Database, Genesis Library and Web of Science). Overall, odds ratio (OR) with 95% CI from fixed and random effects models were determined. Inconsistency was used to asses...
The allele frequencies for eight short tandem repeat (STR) loci HUMvWA, HUMFES/FPS, HUMF13A, HUMF... more The allele frequencies for eight short tandem repeat (STR) loci HUMvWA, HUMFES/FPS, HUMF13A, HUMF13B, HUMTHO1, HUMTPOX, HUMCSF1P0, HUMLPL included in Geneprint TM STR kits were obtained from 234 unrelated individuals in Casablanca. #
This article presents a literature review, which aims to establish a link between the success of ... more This article presents a literature review, which aims to establish a link between the success of pulp revascularization as a new therapeutic approach of teeth with necrotic pulp, and the state of pregnancy in women. The success of pulpal revascularization depends essentially on the availability of stem cells and the presence of growth factors that will direct the differentiation of these cells to a specific cell line. An electronic search was conducted on PUBMED, Cochrane, and Journal of Endodontics using the following keywords: pulp revascularization, pregnancy, growth factors, dental pulp stem cells, . Then, and in order to identify items that would have escaped the electronic search, a manual search was performed from the list of pre-selected items.
Pulpal capping, as it has been used for more than 200 years, helps to preserve the vital pulp and... more Pulpal capping, as it has been used for more than 200 years, helps to preserve the vital pulp and the dentinogenic potential of the tooth. Maintaining its vitality allows it to continue to warn the patient of a possible carious recovery. First made with different materials, it was a resounding success. The evolution of materials, techniques and knowledge of the dentin-pulp complex has gradually improved its results. Nowadays, there are many direct and indirect pulp capping materials. Some, present for more than 50 years, like calcium hydroxide or ZOE, have proven their worth. Others, such as Biodentine or MTA, which are very recent, show promising results. The aim of this paper is to accomplish a literature review concerning this issue.
Background: Antiplatelet drugs are recommended as one of the main medications used in Acute Coron... more Background: Antiplatelet drugs are recommended as one of the main medications used in Acute Coronary Syndromes (ACS) patients. However, an inter-individual variability in platelet response to Clopidogrel has been found in a substantial group of them. Genetic is known be the dominant influencing factor for individual and interethnic variations in drug responses. Polymorphisms in the genes involved in Clopidogrel absorption, biotransformation to the active metabolite, or platelet response to adenosine diphosphate (ADP) have been associated to this impaired response. Interestingly, Multi-Drug Resistance gene-1 (MDR-1) polymorphism influences oral bioavailability of clopidogrel and prognosis of ACS patients. The objectives of our study are, first, to determine the frequency of the C3435T MDR1 polymorphism among Moroccan ACS patients compared to healthy subjects; and second, to assess its effect on Clopidogrel response in a sample of Moroccan ASC patients. Methods and results: 40 ACS pat...
Effect of Allium sativum extract on human PBMC proliferation. CD4 T cell division was evaluated b... more Effect of Allium sativum extract on human PBMC proliferation. CD4 T cell division was evaluated by CFSE staining and flow cytometry when PBMCs were treated with or without A.S. at two different doses in the absence or presence of PHA (a) or Okt-3 mAb (b). CD8 T cell division assessed by CFSE staining and flux cytometry within PBMCs treated with or without A.S. at two doses in the absence or presence of PHA (c) or Okt-3 mAb (d). Data shown are representative of 4 independent experiments. Percentage of cell division was calculated with FlowJo software. Data are represented in mean ± S.D. and were analyzed using the one-way ANOVA test. (DOCX 278 kb)
Background: According to numerous studies, FMS-like tyrosine kinase 3, internal tandem duplicatio... more Background: According to numerous studies, FMS-like tyrosine kinase 3, internal tandem duplication, and the D835 mutation are associated with a poor prognostic clinical outcome in acute myeloid leukemia patients. Detection of the FMS-like tyrosine kinase 3 mutation in patients who present with normal karyotype acute myeloid leukemia helps in both the understanding of the disease and the treatment of patients. This study evaluates the incidence of FMS-like tyrosine kinase 3-internal tandem duplication and FMS-like tyrosine kinase 3-D835 mutation in newly diagnosed patients with normal karyotype acute myeloid leukemia. Methods: This study looked at 33 new cases who presented with normal karyotype acute myeloid leukemia at diagnosis. We collected peripheral blood samples from patients at diagnosis. FMS-like tyrosine kinase 3-internal tandem duplication mutation was detected using polymerase chain reaction and FMS-like tyrosine kinase 3-D835 mutation by restriction fragment length polym...
Breast cancer is the most common cancer affecting women all over the world. In addition to hormon... more Breast cancer is the most common cancer affecting women all over the world. In addition to hormonal and environmental causes, family history is emerging as an important risk factor in the etiology of this disease. The aim of the present study is thus to compare the clinico-pathological features of familial and sporadic breast cancer in Moroccan patients. A comparative retrospective cohort study was conducted on 570 women with familial and sporadic breast cancer who were diagnosed and treated in the Oncology Center of Ibn Rochd University Hospital in 2009. Data on breast cancer risk factors and clinico-pathological characteristics of the tumors were extracted from patients' medical records. Familial cases represented 18.4% of breast cancer patients. The age of onset appears to be earlier in familial breast cancers (P=0.0024). There were no significant differences between familial and sporadic groups according to histological type, tumor size and estrogen receptor status. However,...
Nowadays, many genes are associated with Breast Cancer. In order to understand the cause behind t... more Nowadays, many genes are associated with Breast Cancer. In order to understand the cause behind this particular type of cancer, we chose to study crucial genes previously reported to be involved in its development and mechanisms. Therefore, we worked on BRCA1 and BRCA2 as the main predisposition genes related to 5 to 10% of familial cases and assessed TP53 since it's associated to > 50% types of cancer. Additionally, we measured MDM2 , BAX and CASP3 giving their important role in the internal pathway of apoptosis. For a molecular characterization, we quantified BRCA1 , BRCA2 , TP53 , MDM2 , BAX and CASP-3 mRNA using the qRT-PCR approach in large series of tumor and normal breast tissues of Moroccan patients. We found a significant correlation between the expression of BRCA1 and BRCA2 in normal and tumor tissue. The results showed a positive correlation in the expression of MDM2 between normal and tumor tissue. Furthermore, we detected an elevation of expression of CASP-3 and ...
Acute myeloid leukemia (AML) is a very complex disease that is linked to environmental, genetic a... more Acute myeloid leukemia (AML) is a very complex disease that is linked to environmental, genetic and epigenetic factors. Several Studies have found that aberrations in DNA methylation process play a crucial role in leukemogenesis. The aim of this case control study was to evaluate the association between rs1569686, rs2424913 polymorphisms located in DNMT3B gene and rs7590760 polymorphism located in DNMT3A gene and AML risk in a Moroccan population. MATERIALS AND METHODS The present study was conducted in 142 cases of AML and 179 control subjects from the Moroccan population. Genomic DNA was isolated from whole blood samples by salting-out method and the genotype of the three polymorphisms was determined by the PCR-RFLP technique. RESULTS The study results indicated that rs1569686 polymorphism was significantly associated with the risk of AML in dominant model (OR=1.72, 95 % CI 1.01-2.95, P=0.04), but not in recessive model. In stratified analysis by gender, statistically significant association between the rs2424913 CT genotype and AML was found among males (OR=2.05, 95 % CI 1.00-4.19, P=0.04). Similarly, the rs1569686 TT genotype was associated with an increase risk of AML (OR=3.21, 95 % CI 1.15-8. 98, P=0.02), this association was also found under dominant genetic model (OR=2.47, 95 % CI 1.07-5. 67, P=0.03) among males. However, the rs2424913 polymorphism was not associated with AML. CONCLUSION Our findings have shown that rs1569686 polymorphism might be a risk factor of AML in males. While, the rs2424913 polymorphism was not associated with AML. Further studies with a large sample size are needed to validate our results.
Background: Acute myeloid leukemia (AML) is a complex disease that is linked to genetic and envir... more Background: Acute myeloid leukemia (AML) is a complex disease that is linked to genetic and environmental factors. The gluthatione S-transferase (GST) is a family of enzymes that play a crucial role in the detoxification of carcinogens. These compounds could cause DNA damage, which might lead to the development of cancer. Interindividual inherited differences caused by the presence of single nucleotide polymorphisms (SNPs) in detoxification enzyme, could play a major role in cancer predisposition. The present study aimed to investigate the association between GST gene polymorphisms and AML risk. Methods: The GSTP1 genotype was determined by the PCR-RFLP and multiplex PCR for GSTT1 and GSTM1. Meta-analysis was conducted to evaluate the association between GST gene and the risk of AML. Results: We found that GSTT1 null genotype was significantly associated with the risk of AML. However, GSTM1 and GSTP1 polymorphisms did not influence the AML risk. Subjects carrying the GSTM1 Present, ...
Abstract Cytochrome P450 enzymes play a central role in the phase I biotransformation process of ... more Abstract Cytochrome P450 enzymes play a central role in the phase I biotransformation process of a wide range of compounds, including xenobiotics, drugs, hormones and vitamins. It is noteworthy that these enzymes are highly polymorphic and, depending on the genetic makeup, an individual may have impaired enzymatic activity. Therefore, the identification of genetic variants in these genes could facilitate the implementation of pharmacogenetic studies and genetic predisposition to multifactorial diseases. We have established the frequencies of CYP2B6 (rs3745274; rs2279343) and CYP3A4 (rs2740574) alleles and genotypes in 209 healthy Malian subjects using TaqMan drug metabolism genotyping assays for allelic discrimination. Allele frequencies were 37% for CYP2B6 rs3745274; 38% for CYP2B6 rs2279343; and 75% for CYP3A4 rs2740574 respectively. Overall, the frequencies observed in Mali are statistically comparable to those reported across Africa except North Africa. The major haplotypes in CYP2B6 rs3745274 and CYP2B6 rs2279343 were represented by GA (60.24%) followed by TG (35.36%). We noted a strong linkage disequilibrium between CYP2B6 rs3745274 and CYP2B6 rs2279343 with D’ = 0.91 and r2 = 0.9. The frequencies of the genotypic combinations were 43.5% (GT/AG), 37.3% (GG/AA) and 11.5% (TT/GG) in the combination of CYP2B6-rs3745274 and CYP2B6-rs2279343; 26.8% (GT/CC), 25.4%, (GT/CT), 17.2% and GG/CT in the combination CYP2B6-rs3745274-CYP3A4-rs2740574; 26.8% (AG/CC), 23.9% (AA/CC), 19.1% (AG/CT), and 11% (AA/CT) in the combination CYP2B6-rs2279343-CYP3A4-rs2740574, respectively. The most common triple genotype was GT/AG/CC with 24.9%, followed by GG/AA/CC with 23.9%, GT/AG/CT with 16.7%, and GG/AA/CT with 10%. Our results provide new insights into the distribution of these pharmacogenetically relevant genes in the Malian population. Moreover, these data will be useful for studies of individual genetic variability to drugs and genetic predisposition to diseases.
Abstract Background as it is the case for all kinds of cancer; lung cancer is a multifactorial di... more Abstract Background as it is the case for all kinds of cancer; lung cancer is a multifactorial disease. The interaction between both Exposures to different carcinogens and individual genetic backgrounds modulate the disease risk. Cytochrome P450 family is one of the main enzymes involved in the metabolism of these carcinogens. Therefore, polymorphisms of genes encoding for the cyp450 enzymes can be responsible for the inter-individual differences in lung cancer susceptibility. In this study, we chose to focus on the Cyp2c19, as one of the crucial cyp450 enzymes associated with metabolism of a number of drugs and xenobiotics and its association with the lung cancer risk. Methods peripheral blood from a total of 115 Moroccan patients diagnosed with lung cancer and 105 healthy subjects was collected. The genotyping of CYP2C19*2 and CYP2C19*3 polymorphisms was carried out using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technic. Results we found that the frequency of both CYP2C19*2 (GA+AA) genotype and CYP2C19*A allele were significantly more frequent in lung cancer patients than that in control subjects (24.3% vs 13.3%; p=0.04 and 14.35% vs 7.15%; p=0.01 respectively). We also found that the CYP2C19*3 A allele was only found in lung cancer patient with a frequency of 10% (p= 0.007). Consequently, the frequency of the CYP2C19*3 (GA+AA) genotype was also significantly more prevalent in lung cancer patients than that in controls (20% vs 0.00%; p=0.005). We also found that smoking is associated to a higher lung cancer risk in participants carrying CYP2C19*3 or CYP2C19*2 GG genotypes (p Conclusion These findings indicate that the CYP2C19*2 and CYP2C19*3 polymorphisms are significantly associated with lung cancer in Moroccan population. In addition, that the coexistence of CYP2C19*3 with smoking increased lung cancer risk even more.
Abstract Background Low-Grade Gliomas are the most common brain tumor in children. They are chara... more Abstract Background Low-Grade Gliomas are the most common brain tumor in children. They are characterized by a broad spectrum of very heterogeneous tumor subtypes. Their current definition is mainly based on histological criteria which represents an important limit because these classifications suffer from a lack of precision. Recent advances in genomics allow us to considerably deepen our knowledge of the biology of these tumors in order to enrich their current classification. Aim In this work, we studied the frequency of KIAA1549/BRAF fusion in 89 pLGG tissues of Moroccan patients with Pediatric Low-Grade Gliomas, using PCR-RFLP and Fluorescence In Situ Hybridization and we compared our results with the frequency of KIAA1549/BRAF fusion in 123 pHGG tissues of Moroccan patients with Pediatric High-Grade Gliomas. Methodology We studied the frequency of KIAA1549/BRAF fusion in 89 pLGG tissues, using PCR-RFLP and Fluorescence In Situ Hybridization. Data was analyzed by using IBM SPSS software v24. Results 32 patients with pLGG had a positive KIAA1549/BRAF fusion, compared to 57 with a negative KIAA1549/BRAF fusion by using PCR-RFLP and Fluorescence In Situ Hybridization. Based on our findings, the frequency of KIAA1549/BRAF fusion in Moroccan patients with Pediatric Low-Grade Gliomas is 36.0% in the pLGGs and there is significant relationship between the presence of KIAA1549/BRAF fusion in pLGGs and pHGGs (P Conclusion We hope that the results of this study will contribute to the improvement of the molecular and histopathological classification of Pediatric Low-Grade Gliomas (pLGGs) and bring innovations to patient treatment by establishing new clinical trials and experimental studies, as well as a more precise categorization for epidemiological purposes.
Triple-negative breast cancer (TNBC) can be distinguished from other breast malignancies by the l... more Triple-negative breast cancer (TNBC) can be distinguished from other breast malignancies by the lack of expression of estrogen receptors (ER), progesterone receptors (PR) as well as human epidermal growth factor receptor 2 (HER2). TNBC is associated with adverse clinical outcomes and high risk of metastasis. Currently, several clinical and translational reports are focusing on developing targeted therapies for this aggressive cancer. In addition to approved targeted drugs such as poly(ADP-ribose) polymerase inhibitors (PARPi) and immune-checkpoint inhibitors, platinum-based chemotherapy is still a cornerstone therapeutic option in TNBC. However, despite the observed improved outcomes with platinum- based chemotherapy in TNBC, there is still a large proportion of patients who do not respond to this treatment, hence, the need for predictive biomarkers to stratify TNBC patients and therefore, avoiding unwanted toxicities of these agents. With the emergence of genetic testing, several r...
Background Breast cancer, the most common tumor in women in Mali and worldwide has been linked to... more Background Breast cancer, the most common tumor in women in Mali and worldwide has been linked to several risk factors including genetic factors, such as the PIN3 16-bp duplication polymorphism of TP53 gene. The aim of our study was to evaluate the role of the PIN3 16-bp duplication polymorphism in the susceptibility to breast cancer in the Malian population and to perform a meta-analysis to better understand the correlation with data from other populations.Methods We analyzed the PIN3 16-bp duplication polymorphism in blood samples of 60 Malian women with breast cancer and 60 healthy appearing Malian women using PCR. In addition, we performed a meta-analysis of data from case-control studies published in articles retrieved from international databases (Pubmed, Harvard University Library, Genetics Medical Literature Database, Genesis Library and Web of Science). Overall, odds ratio (OR) with 95% CI from fixed and random effects models were determined. Inconsistency was used to asses...
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