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The symptoms of SARS-CoV-2 infection vary widely, ranging from asymptomatic cases to severe forms marked by acute respiratory distress syndrome, multi-organ damage, and fatalities. Studies indicate a correlation between specific genes and susceptibility to SARS-CoV-2 infection and disease severity, particularly involving variants in genes linked to inflammation and immune responses. The objective of this study is to investigate the association between rs1800795 (- 174 G > C) and rs1800797 (- 597 A > G) variants in the interleukin-6 (IL-6) promoter region and susceptibility to SARS-CoV-2 infection. Additionally, we aim to explore their correlation with COVID-19 severity in a Moroccan population. In this case-control study, we enrolled 270 unvaccinated COVID-19 patients, consisting of 132 with severe COVID-19 and 138 with asymptomatic-moderate COVID-19. Additionally, we included 339 SARS-CoV-2-negative group. Genotyping of rs1800795 and rs1800797 polymorphisms of the IL-6 gene was performed using predesigned TaqMan SNP genotyping. The median age of SARS-CoV-2-negative controls was 50 years, while severe COVID-19 cases exhibited a median age of 61 years. Additionally, individuals with asymptomatic to moderate COVID-19 had a median age of 36 years. We observed a significant age difference between severe and mild COVID-19 patients (p < 0.0001), and an association was noted between gender and the severity of COVID-19 (p = 0.011). The allele and genotype frequencies of the IL-6 - 597G > A and - 174G > C variants did not show significant associations with susceptibility to SARS-CoV-2 infection (p > 0.05). However, further analysis revealed that the linkage disequilibrium between rs1800797 and rs1800795 indicated that individuals with the GC* haplotype (OR = 0.04, 95% CI 0.01-0.30, p = 0.001) and AG* haplotype (OR = 0.11, 95% CI 0.03-0.46, p = 0.002) were significantly associated with protection against SARS-CoV-2 infection. Moreover, in the overdominant model, the IL-6 - 174 G/C genotype was found to be protective against the development of severe disease compared to those with the G/G-C/C genotypes (p = 0.03; OR = 0.41, 95% CI 0.18-0.96). However, correlations between complete blood count markers, hematological markers, D-dimer, C-reactive protein, and ferritin levels according to - 597 A > G and - 174G > C genotypes showed no significant differences (all p > 0.05). Our findings provide valuable insights into the pathogenesis of COVID-19, suggesting that genetic variations at the IL-6 gene may contribute to the susceptibility to severe SARS-CoV-2 infection within the Moroccan population.
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COVID-19 , Predisposição Genética para Doença , Interleucina-6 , Polimorfismo de Nucleotídeo Único , SARS-CoV-2 , Índice de Gravidade de Doença , Humanos , COVID-19/genética , COVID-19/virologia , Interleucina-6/genética , Feminino , Masculino , Estudos de Casos e Controles , Marrocos , Pessoa de Meia-Idade , Adulto , Regiões Promotoras Genéticas , Idoso , Frequência do Gene , HaplótiposRESUMO
BACKGROUND: Acute lymphoblastic leukemia is the most common childhood cancer, with an 80% frequency in children between 1 and 10 years old. The outcome and prognosis of acute lymphoblastic leukemia in children depends on various factors, such as age, clinical and biological features, and cytogenetic factors. CASE PRESENTATION: We report the case of a pediatric patient, a 4-year-old Moroccan female who was referred to the Hematology and Oncology Department of 20 August 1953 Hospital in Casablanca and diagnosed with B-cell acute lymphoblastic leukemia associated with a rare genetic chromosomal abnormality. CONCLUSION: Translocation (1;4)(p21;p15) is a relatively rare chromosomal abnormality found in human leukemia and was never described isolated in pediatric B-cell acute lymphoblastic leukemia patients. It showed a good evolution by complete remission and recovery of this patient after receiving all chemotherapy and after 8 years of follow-up.
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Leucemia-Linfoma Linfoblástico de Células Precursoras , Translocação Genética , Pré-Escolar , Feminino , Humanos , Aberrações Cromossômicas , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , PrognósticoRESUMO
Variants in SCN8A are associated with several diseases, including developmental and epileptic encephalopathy, intermediate epilepsy or mild-to-moderate developmental and epileptic encephalopathy, self-limited familial infantile epilepsy, neurodevelopmental delays with generalized epilepsy, neurodevelopmental disorder without epilepsy, hypotonia, and movement disorders. Herein, we report an 8-year-old Moroccan boy with intermediate epilepsy of unknown origin, intellectual disability, autism spectrum disorder, and hyperactivity. The patient presented a normal 46, XY karyotype and a normal comparative genomic hybridization profile. Whole-exome sequencing was performed, and heterozygous variants were identified in KCNK4 and SCN8A. The SCN8A variant [c.4499C > T (p.Pro1500Leu)] was also detected in the healthy mother and was classified as a variant of uncertain clinical significance. This variant occurs in a highly conserved domain, which may affect the function of the encoded protein. More studies are needed to confirm the pathogenicity of this novel variant to establish the effective care, management, and genetic counselling of affected individuals.
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Transtorno do Espectro Autista , Epilepsia , Deficiência Intelectual , Transtornos dos Movimentos , Masculino , Criança , Humanos , Transtorno do Espectro Autista/complicações , Hibridização Genômica Comparativa , Epilepsia/complicações , Deficiência Intelectual/genética , Mutação , Canal de Sódio Disparado por Voltagem NAV1.6/genéticaRESUMO
BACKGROUND: Chronic hepatitis B virus (CHB) infection is still incurable a major public health problem. It is yet unclear how host genetic factors influence the development of HBV infection. The peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A) has been shown to regulate hepatitis B virus (HBV). Several reports found that PPARGC1A variants are involved in a number of distinct liver diseases. Here we investigate whether the PPARGC1A rs8192678 (Gly482Ser) variant is involved in the spontaneous clearance of acute HBV infection and if it participates in chronic disease progression in Moroccan patients. METHODS: Our study included 292 chronic hepatitis B (CHB) patients and 181 individuals who spontaneously cleared-HBV infection. We genotyped the rs8192678 SNP using a TaqMan allelic discrimination assay and then explored its association with spontaneous HBV clearance and CHB progression. RESULTS: Our data showed that individuals carrying CT and TT genotypes were more likely to achieve spontaneous clearance (OR = 0.48, 95% CI (0.32-0.73), p = 0.00047; OR = 0.28, 95% CI (0.15-0.53), p = 0.00005, respectively). Subjects carrying the mutant allele T were more likely to achieve spontaneous clearance (OR = 0.51, 95% CI (0.38-0.67), P = 2.68E-06). However, when we investigated the impact of rs8192678 on the progression of liver diseases, we neither observe any influence (p > 0.05) nor found any significant association between ALT, AST, HBV viral loads, and the PPARGC1A rs8192678 genotypes in patients with CHB (p > 0.05). CONCLUSION: Our result suggests that PPARGC1A rs8192678 may modulate acute HBV infection, and could therefore represent a potential predictive marker in the Moroccan population.
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Vírus da Hepatite B , Hepatite B Crônica , Humanos , Genótipo , Vírus da Hepatite B/genética , Hepatite B Crônica/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Polimorfismo de Nucleotídeo Único , PPAR gama/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
INTRODUCTION: Complete remission (CR) in patients with acute myeloid leukemia (AML) is still morphologicaly defined, thus corresponding to a wide range of tumor burden. OBJECTIVES: we aimed to evaluate the residual disease (MRD) status in patients with AML, as well as perform a molecular analysis of the FLT3/ITD gene in patients with normal karyotype. MATERIAL AND METHODS: adult patients with AML, diagnosed according to the WHO 2016 criteria, were included. MRD was detected using flow cytometric techniques after induction treatment resulting in CR. RESULTS: thirty patients met our inclusion criteria. 83 % of them had an intermediate risk status, 67 % of which (20/30) having a normal karyotype. MRD and leukemic stem cell (LSC) positivity in this group was predominant with considerable decrease in benign progenitor count. The relapse-free survival (RFS) in the group of MRD negative patients with normal cytogenetics and non-mutated FLT3 gene was better than the RFS in all of our patients studied. CONCLUSION: MRD and LSC are powerful prognostic factors for relapse. They should be routinely integrated to guide better management of AML.
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Leucemia Mieloide Aguda , Adulto , Humanos , Prognóstico , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Indução de Remissão , Cariótipo , Mutação , Neoplasia Residual/diagnóstico , Neoplasia Residual/genética , Tirosina Quinase 3 Semelhante a fms/genéticaRESUMO
Methylenetetrahydrofolate reductase (MTHFR) plays a major role in the metabolism of folates and homocysteine, which in turn can affect gene expression and ultimately promote the development of breast cancer. Thus, mutations in the MTHFR gene could influence homocysteine, methionine, and S-adenosylmethionine levels and, indirectly, nucleotide levels. Imbalance in methionine and S-adenosylmethionine synthesis affects protein synthesis and methylation. These changes, which affect gene expression, may ultimately promote the development of breast cancer. We therefore hypothesized that such mutations could also play an important role in the occurrence and pathogenesis of breast cancer in a Malian population. In this study, we used the PCR-RFLP technique to identify the different genotypic profiles of the C677T MTHFR polymorphism in 127 breast cancer women and 160 healthy controls. The genotypic distribution of the C677T polymorphism in breast cancer cases was 88.2% for CC, 11.0% for CT, and 0.8% for TT. Healthy controls showed a similar distribution with 90.6% for CC, 8.8% for CT, and 0.6% for TT. We found no statistical association between the C677T polymorphism and breast cancer risk for the codominant models CT and TT (p > 0.05). The same trend was observed when the analysis was extended to other genetic models, including dominant (p = 0.50), recessive (p = 0.87), and additive (p = 0.50) models. The C677T polymorphism of MTHFR gene did not influence the risk of breast cancer in the Malian samples.
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Neoplasias da Mama , Metilenotetra-Hidrofolato Redutase (NADPH2) , Feminino , Humanos , Neoplasias da Mama/genética , Homocisteína , Mali , Metionina , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , S-AdenosilmetioninaRESUMO
Rett syndrome (RTT) is a rare X-linked syndrome that predominantly affects girls. It is characterized by a severe and progressive neurodevelopmental disorder with neurological regression and autism spectrum features. The Rett syndrome is associated with a broad phenotypic spectrum. It ranges from a classical Rett syndrome defined by well-established criteria to atypical cases with symptoms similar to other syndromes, such as Angelman syndrome. The first case of a Moroccan female child carrying a R306X mutation in the MECP2 (Methyl-CpG-Binding Protein 2) gene, with an unusual manifestation of Rett syndrome, is presented here. She showed autistic regression, behavioral stagnation, epilepsy, unmotivated laughter, and craniofacial dysmorphia. Whole exome sequencing revealed a nonsense mutation (R306X), resulting in a truncated, nonfunctional MECP2 protein. The overlapping phenotypic spectrums between Rett and Angelman syndromes have been described, and an interaction between the MECP2 gene and the UBE3A (Ubiquitin Protein Ligase E3A) gene pathways is possible but has not yet been proven. An extensive genetic analysis is highly recommended in atypical cases to ensure an accurate diagnosis and to improve patient management and genetic counseling.
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Breast Cancer remains, according to the World Health Organization, the most complex disease cancer in 2021 in the world and the most common cause of death among women. Based on unequivocal scientific data, the establishment of an operative program for prevention could save lives of millions women suffering from breast cancer. In this update review, we highlight the major risk factors related to breast cancer investigated in women over the last 5 years. Thus, we clarify the involvement of these risk factors in the occurrence and growth of breast cancer. Investigations of 15 studies (n = 1,254,418; six case-control studies, five cohort studies, three prospective studies, and one meta-analysis) revealed that age, family history, obesity, use of oral contraceptives, status menopausal, smoking, alcohol consumption, lifestyle, and genetics factors are significantly linked to breast cancer. Additional studies are needed to corroborate these outcomes and initiate new practices aimed at preventing breast cancer.
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Neoplasias da Mama , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , Neoplasias da Mama/epidemiologia , Feminino , Humanos , Estilo de Vida , Estudos Prospectivos , Fatores de RiscoRESUMO
OBJECTIVES: The main objective of this study was to evaluate the effect of CYP2B6 and CYP3A4 polymorphisms on the virological and immunologic responses of HIV patients. A total of 153 HIV-positive patients were enlisted for the study. PATIENTS AND METHODS: Viral load and median CD4 T cell counts were evaluated at baseline and month 6 (M6). Samples were identified using TaqMan genotyping assays. RESULTS: The AG in CYP2B6 rs2279343 was associated with VLS compared to homozygous AA. In the dominant model, the AG/GG genotypes were associated with VLS compared to the AA genotype. Moreover, in overdominant model, the AG genotype was associated with VLS compared to AA/GG. Regarding immunological response, only the AG in SNP rs2279343 CYP2B6 was associated with an increase in CD4 cell count between baseline and M6. In CYP2B6 rs3745274, the CD4 cell count at M6 was higher than that of baseline for GG carriers and for GT carriers. In CYP3A4 rs2740574, the TC carriers showed a higher median CD4 count at M6 compared to that of the baseline count, as well as for CC carriers. The best genotypes combination associated with CD4 cell count improvement were AA/AG in SNP rs2279343 and GG/GT in SNP rs3745274. CONCLUSION: Our findings support the fact that CYP2B6 rs2279343 could help in the prediction of VLS and both SNPs rs3745274 and rs2279343 in CYP2B6 and CYP3A4 rs2740574 were associated with immune recovery in Malian HIV-positive patients.
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Fármacos Anti-HIV , Benzoxazinas , Ciclopropanos , Infecções por HIV , Alcinos , Fármacos Anti-HIV/farmacologia , Benzoxazinas/farmacologia , Ciclopropanos/farmacologia , Citocromo P-450 CYP2B6/genética , Inibidores do Citocromo P-450 CYP2B6/farmacologia , Citocromo P-450 CYP3A/genética , Genótipo , Infecções por HIV/tratamento farmacológico , Infecções por HIV/enzimologia , Infecções por HIV/genética , Humanos , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: Hepatitis B Virus (HBV) is the most common cause of chronic liver disease worldwide. The mechanisms that regulate HBV viral replication remain poorly defined. Here, we show that blocking of the neddylation elicits antiviral effect against HBV replication, indicating that NEDD8 supports viral production. METHODS AND RESULTS: To explore role of neddylation, HBV-replicating HepG2.2.15.7 cells and HBV-infected HepG2-hNTCP-30 cells were treated with siNEDD8 and MLN4924, a potent and selective NEDD8-activating enzyme inhibitor. Cell viability, intracellular and extracellular HBV DNA, covalently closed circular DNA (cccDNA), HBsAg, HBeAg, and HBcrAg were measured to assess the consequences of the various treatments on viral replication. Our data showed that HBV infection increased NEDD8 expression in human liver cell lines. Symmetrically, NEDD8 knockdown by siRNA or MLN4924 treatments decreased HBV replication in HepG2.2.15.7 and HepG2-hNTCP-30 cells. Notably, HBsAg, and HBeAg secretions were strongly suppressed in the culture supernatants, but not the HBcrAg. These results indicate that the suppression of NEDD8 decreases HBV replication. However, cccDNA steady level confirms once again its persistence and longevity in chronic infection. CONCLUSION: The manipulation of the neddylation pathway can thus provide new tools interfering with HBV persistence as well as novel therapeutic strategies against chronic hepatitis B.
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Antivirais/farmacologia , Ciclopentanos/farmacologia , Vírus da Hepatite B/fisiologia , Proteína NEDD8/metabolismo , Pirimidinas/farmacologia , RNA Interferente Pequeno/farmacologia , Sobrevivência Celular/efeitos dos fármacos , DNA Viral/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Antígenos de Superfície da Hepatite B/genética , Antígenos E da Hepatite B/genética , Vírus da Hepatite B/efeitos dos fármacos , Humanos , Proteína NEDD8/genética , Replicação Viral/efeitos dos fármacosRESUMO
Common variable immunodeficiency (CVID) is one of the most prevalent primary immunodeficiencies. It is characterized by hypogammaglobulinaemia, increased susceptibility to infections and impaired vaccine responses. CVID has an important, clinical, immunological and genetic heterogeneity. A minority of patients present with monogenic forms in CVID, unlike other primary immunodeficiencies. With the development of new technologies in genetics, including next generation sequencing, the number of identified genes in CVID is increasing. Therefore, CVID is now considered as an umbrella disease, gathering distinct pathological entities. It is currently recognized that CVID is a complex polygenic rather than a monogenic syndrome. A multi-omic approach combining genomics, epigenetics and proteomics will shed light on CVID complex pathophysiology, which still enigmatic. This integrative approach will also offer more targeted therapies, and therefore a personalized medicine. This review aims to discuss current knowledge concerning the genetic and molecular bases of CVID as well as their application in clinical practice.
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Imunodeficiência de Variável Comum , Imunodeficiência de Variável Comum/diagnóstico , Imunodeficiência de Variável Comum/genética , Predisposição Genética para Doença , Genômica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Medicina de PrecisãoRESUMO
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'â=â0.91 and r2â=â0.9. 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.
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Alelos , Genótipo , Haplótipos/genética , Adolescente , Adulto , Idoso , Citocromo P-450 CYP2B6/genética , Citocromo P-450 CYP3A/genética , Feminino , Humanos , Malásia/etnologia , Masculino , Pessoa de Meia-Idade , Farmacogenética/métodosRESUMO
Primary congenital glaucoma (PCG) is a rare and severe form of glaucoma and is usually transmitted as an autosomal-recessive disease. However, PCG is more common in certain ethnic and geographic groups where consanguineous relationships are common. The importance of this review is to inspect the mutations in the cytochrome P450 1B1 gene (CYP1B1) and to highlight the interest of the genetic study of CYP1B1 mutations. An in-depth study was carried out by the following search engines: PubMed, Scopus, clinic key and direct science for articles that have been published from 2011 until 2020. One hundred and sixty-one mutations were found in 1641 tested patients and three families, including 78 novel mutations. We identified a no significant difference in the sex ratio and the bilaterality was reported in the majority of patients. We have shown through this study that inbreeding plays an important role in the pathogenesis of PCG transmission compared to the sporadic mutations that have been found in some cases. The majority of the included studies were from ASIA (64.3%), followed by Europe (17.85%), America (10.71%) and Africa (7.14%). The first and most common mutation in our study is 182 G>A (p.Gly61Glu). It was identified in Iran, Portugal and Saudi Arabia and for the first time in Brazil and Vietnam. The greatest number of mutations in common is p.Gly61Glu. Mainly within five countries: Iran, Portugal, Saudi Arabia, Brazil and Vietnam. The first step in PCG screening should be a genetic test looking for founder and common mutation coupled with a clinical examination.
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Glaucoma , Hidroftalmia , Citocromo P-450 CYP1B1/genética , Análise Mutacional de DNA , Humanos , Hidroftalmia/genética , Mutação , LinhagemRESUMO
Noncoding RNAs have emerged as key regulators of the genome upon gene expression profiling and genome-wide sequencing. Among these noncoding RNAs, microRNAs are short noncoding RNAs that regulate a plethora of functions, biological processes and human diseases by targeting the messenger RNA stability through 3'UTR binding, leading to either mRNA cleavage or translation repression, depending on microRNA-mRNA complementarity degree. Additionally, strong evidence has suggested that dysregulation of miRNAs contributes to the etiology and progression of human cancers, such as lung cancer, the most common and deadliest cancer worldwide. Indeed, by acting as oncogenes or tumor suppressors, microRNAs control all aspects of lung cancer malignancy, including cell proliferation, survival, migration, invasion, angiogenesis, cancer stem cells, immune-surveillance escape, and therapy resistance; and their expressions are often associated with clinical parameters. Moreover, several deregulated microRNAs in lung cancer are carried by exosomes and microvesicles and secreted in body fluids, mainly the circulation, where they conserve their stable forms. Subsequently, seminal efforts have been focused on extracellular microRNAs levels as noninvasive diagnostic and prognostic biomarkers in lung cancer. In this review, focusing on recent literature, we summarize the deregulation, mechanisms of action, functions and highlight clinical applications of miRNAs for better management and design of future lung cancer targeted therapies.
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Exossomos , Neoplasias Pulmonares , MicroRNAs , Biomarcadores Tumorais/genética , Exossomos/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , MicroRNAs/genética , RNA MensageiroRESUMO
BACKGROUND: Essential hypertension (EH) results from a complex interaction between environmental factors and an individual's genetic background. AIM: To assess the relationship between polymorphisms in GSTM1 and GSTT1 and the risk of EH. SUBJECTS AND METHODS: A multiplex-PCR was used to identify the genotypic profiles of GSTM1 and GSTT1 in 160 patients and 210 controls. RESULTS: The frequency of GSTM1-null genotype was higher in patients younger than 61 years when compared to those over 61 years. Interestingly, GSTT1-null was significantly associated with the risk of EH (OR 4; 95% CI 2.6-6.3; p < 0.0001). While GSTM1-null showed no trend (OR 0.7; 95% CI 0.5-1.1, p = 0.12). Individuals carrying the combined GSTT1-null/GSTM1-null were 2.4 times more at risk for hypertension compared to those harbouring the combined GSTT1-present/GSTM1-present genotype (OR 2.4; 95% CI 1.3-4.4; p = 0.005). Additionally, the presence of the combined GSTT1-null/GSTM1-present was associated with an increased risk of EH compared to GSTT1-present/GSTM1-present carriers (OR 6.75; 95% CI 3.4-13.2; p < 0.0001). CONCLUSION: This study showed that the GSTT1-null alone or in interaction with GSTM1-present or GSTM1-null was associated with a higher risk of hypertension. Moreover, the GSTM1-null seems to be associated with the age of onset of hypertension.
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Hipertensão Essencial , Predisposição Genética para Doença , Glutationa Transferase , Estudos de Casos e Controles , Hipertensão Essencial/genética , Genótipo , Glutationa Transferase/genética , Humanos , Pessoa de Meia-Idade , Polimorfismo Genético , Fatores de RiscoRESUMO
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.
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DNA (Citosina-5-)-Metiltransferases , Estudos de Casos e Controles , DNA (Citosina-5-)-Metiltransferases/genética , Metilação de DNA , DNA Metiltransferase 3A , Predisposição Genética para Doença , Genótipo , Humanos , Leucemia Mieloide Aguda , Polimorfismo de Fragmento de Restrição , Fatores de Risco , DNA Metiltransferase 3BRESUMO
Cytogenetic and iFISH plays a major part in the diagnosis of the MM and have an important prognostic significance. 10-15% of patients with amyloidosis will also have multiple myeloma (MM). Few studies have addressed the clinical and cytogenetic features of patients with AL amyloidosis with concurrent multiple myeloma. This study of MM case in which we found a near tetraploid complex karyotype with the t(11;14) (q13;q32) abnormality in cytogenetic analysis and the presence of t(4;14) and del(17p) by iFISH, referred to several studies which showed the translocation t(11;14) as the most frequent abnormality in both AL amyloidosis and MM.
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The human multidrug resistance MDR1 gene plays a crucial role in the absorption, transport, metabolism and elimination of harmful compounds. An impaired metabolism of these compounds related to genetic polymorphism may cause cancer such as acute myeloid leukemia AML. OBJECTIVE: The present study investigated the relationship between C1236T polymorphism and the risk of AML development in a sample of Moroccan population. METHODS: The present case-control study included 131 AML patients and 136 healthy controls. The MDR1 C1236T polymorphism was identified by PCR-RFLP method. Meta-analysis was performed to discuss our results. Statistical analyses were performed using SPSS, MetaGenyo and MedCalc. RESULTS: A positive association was found between the 1236TT mutant genotype and the risk of AML (OR 2.39; 95% CI 1.02-5.57, p= 0.04) compared to the wild type 1236CC. In addition, the recessive model revealed that carriers of 1236TT mutant genotype were more exposed to develop AML when compared to the combined 1236CC/CT genotype (OR: 2.27, CI: 1.01-5.05, p=0.04). The clinical parameters of AML showed no significant association. Meta-analysis demonstrated no statistically significant association between this polymorphism and AML susceptibility. CONCLUSION: Our study suggests that the MDR1C1236T polymorphism appears to be associated with the risk of AML. Further studies, including a large sample size, are needed to confirm these findings.
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Biomarcadores Tumorais/genética , Predisposição Genética para Doença , Leucemia Mieloide Aguda/epidemiologia , Polimorfismo de Nucleotídeo Único , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Leucemia Mieloide Aguda/genética , Masculino , Pessoa de Meia-Idade , Marrocos/epidemiologia , Prognóstico , Fatores de RiscoRESUMO
BACKGROUND: Multiple myeloma (MM) is a disease characterized by heterogeneous clinical presentations as well as complex genetic and molecular abnormalities. In MM, cytogenetic analysis is a challenge because of the low proliferation of malignant plasma cells. Thus, interphase fluorescence in situ hybridization (FISH), performed on sorted plasma cells detected abnormalities independently of a proliferative and infiltrative index. The purpose of this study was to explore, for the first time, the cytogenetic and molecular genetics features in Moroccan patients with multiple myeloma referred exclusively to National Reference Laboratory and to determine their risk stratification based on these features. METHODS: We performed cytogenetic analysis on 93 MM cases, all patients were subjected to FISH analysis, among which 45 patients have benefited from both FISH analysis and standard karyotype. RESULTS: Karyotype was normal in 78% (35/45) while, it was complex with varied structural and numerical abnormalities in 22% (10/45) of all patients, among which Hyperdiploid karyotype was found in 9% (n = 4 cases) and nonhyperdiploid in 13% (n = 6 cases). The most common numerical abnormalities were gains of chromosomes 3, 5, 9, 15, and 19. Whole chromosome losses were also frequent, affecting chromosomes X, 3, 14, 16 and 22. FISH analysis detected abnormalities in 50% of cases. The translocation t(4;14) and dup (1q) were the most frequent types of anomalies (14% and 13% respectively), followed by (17p) deletion and 14q32/IGH translocations with an undetermined origin (12% each) then the (1p) deletion (4%). For the normal karyotypes, FISH revealed chromosome abnormalities in 46%. CONCLUSION: This study compares the results of cytogenetic analysis of chromosomal abnormalities in the Moroccan population with other countries. ½ patient showed at least one type of molecular genetic abnormalities. Therefore, the introducing of the cytogenetic analysis is obligatory in the diagnosis of multiple myeloma.