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1.
Mol Biol Rep ; 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31650384

RESUMO

Glutathione S-transferase genes, known to be highly polymorphic, are implicated in the process of phase II metabolism of many substrates, including xenobiotics, anticancer and anti-infective drugs. The detoxification activity is linked to individual genetic makeup. Therefore, the identification of alleles and genotypes in these genes within a population may help to better design genetic susceptibility and pharmacogenetic studies. We performed the present study to establish the frequencies of the GSTM1, GSTT1, and GSTP1 c. 313A > G (rs1695) polymorphisms in 206 individuals of the Malian healthy population. GSTM1 and GSTT1 were genotyped by using multiplex polymerase chain reaction, whereas genotypes of GSTP1 were identified by polymerase chain reaction followed by restriction fragment length polymorphism. The frequencies of GSTM1-null and GSTT1-null genotypes were respectively 24.3 and 41.3%. The observed genotype frequencies for GSTP1 were 25.73% homozygous wild-type AA, 49.03% heterozygous AG and 25.24% homozygous mutant GG. The frequency of GSTP1-A allele was 50.24% versus 49.76% for the GSTP1-G allele. The distribution of these three genes was homogeneous between men and women (p > 0.05). We found no statistical association between the presence of a particular profile of GSTM1 or GSTT1 with the genotypes of GSTP1 (p > 0.05). Nevertheless, we noticed that the majority of the individuals harboring the GSTM1-present or the GSTT1-present harbor also the GSTP1-AG genotype. In addition, the triple genotype GSTM1-present/GSTT1-present/AG was the most frequent with 25.2%. Our findings will facilitate future studies regarding genetic associations of multifactorial diseases and pharmacogenetic, thus opening the way to personalized medicine in our population.

2.
Lung ; 197(5): 601-608, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31468132

RESUMO

PURPOSE: Lung cancer is known to be a complex multifactorial disease, involving both genetic and environmental factors. The study of the different signaling pathways and the identification of the genes involved, will contribute to further understanding the pathogenesis of the disease, thus allowing the development of appropriate targeted treatments. Recently, the link between cancer and inflammation has become more evident and inflammation has been proposed as the seventh hallmark of cancer. Previous studies have suggested that key cytokines involved in inflammation may have an important role in the etiology of lung cancer. The aim of this study was to investigate whether common variants in inflammation-related genes: IL-6, IL6-R, and IL6-ST, influence lung cancer risk in Moroccan population. MATERIALS AND METHODS: Single nucleotide polymorphisms (SNPs) in IL-6, IL6-R, and IL6-ST genes were assessed in 120 controls and 120 patients with confirmed lung cancer diagnosis. Genotyping analysis was performed with the TaqMan® allelic discrimination technology. The results were analyzed using SPSS 24.0 software. RESULTS: Among the studied SNPs, we found a significant association for the IL-6 (rs2069840) (OR = 1.63; 95% confidence interval 1.08-2.47; p = 0.01). No significant association was observed for the remaining SNPs of IL-6R (rs2228145) and IL-6ST (rs2228044) genes. CONCLUSION: Our results suggest the IL-6 (rs2069840) polymorphism may influence the occurrence of lung cancer in Moroccan patients.

3.
Gene ; 705: 36-43, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31004715

RESUMO

The study of EGFR gene mutational profile in NSCLC patients has a special clinical significance in the selection of patients for tyrosine-kinase inhibitors therapy. From 2017, the targeted therapy started to be accessible in public sector in Morocco, thus, the implementation of techniques for the molecular characterization of EGFR mutations in the laboratories became a necessity. The aim of this study was to present targeted methods "ADx-ARMS technology and the Idylla™ system" for the identification of EGFR mutational profile, methods that can be implemented in our clinical laboratories for routine analysis instead of outsourcing analysis to other countries. We conducted this study by processing 239 cases of NSCLC patients. Using the DNA extracted from the FFPE tissue, we evaluated somatic mutations in exons 18 to 21 of the tyrosine-kinase domain of EGFR gene by HRM-PCR combined to real time PCR "ADx-ARMS technology" and Idylla™ system. These sensitive methods showed that among the positive mutant cases, the distribution of mutations was as follows: 70% of patients having a deletion in exon 19, 15% in exon 21 (L858R), 7.5% in exon 20 and 7.5% in exon 18 (G719X). All of the positive EGFR mutations cases were adenocarcinoma and 42.1% of them were smokers. These results show the need to incorporate a quick and efficient method for the identification of EGFR mutation into routine practice in our laboratories, allowing more patients to benefit from targeted therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Análise Mutacional de DNA/métodos , Neoplasias Pulmonares/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Testes Diagnósticos de Rotina , Receptores ErbB/genética , Éxons , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Marrocos , Mutação
4.
Neurosci Lett ; 703: 1-4, 2019 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-30849405

RESUMO

Myoclonus-Dystonia (M-D) is a rare autosomal-dominant movement disorder characterized by myoclonic jerks in combination with dystonia and psychiatric features. Mutations in the Epsilon-sarcoglycan (SGCE, DYT11) gene have been found to cause M-D in 30%-50% of familial M-D. Sporadic cases have also been reported. The aim of study was to investigate whether the M-D phenotype is associated with the existence of SGCE mutations in Moroccan sporadic patients with M-D syndrome. The study included 12 M-D patients. We sequenced the entire coding region of the SGCE gene. We identified two different heterozygous SGCE mutations (c.769A > C ; c.391-3T > C). Our finding confirm that SGCE mutations can occur in sporadic patients when the phenotype is consistent with M-D. Further functional studies are needed to show how changes in SGCE protein function lead to the M-D phenotype.


Assuntos
Distúrbios Distônicos/genética , Sarcoglicanas/genética , Adolescente , Adulto , Criança , Feminino , Estudos de Associação Genética , Humanos , Masculino , Marrocos , Mutação , Adulto Jovem
5.
BMC Res Notes ; 11(1): 783, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30384859

RESUMO

OBJECTIVE: In view of the discrepant data regarding the association between the protein tyrosine phosphatase non-receptor 22 (PTPN22) rs2476601 (R620W, 1858C→T) polymorphism and susceptibility to autoimmune diseases including inflammatory bowel diseases (IBD), we investigated whether this functional single-nucleotide polymorphism influences IBD risk in a group of Moroccan patients. RESULTS: This is the first report on the prevalence of PTPN22 (R620W) variant in a Moroccan cohort. No evidence of statistically significant differences was observed when the PTPN22 (R620W) allele and genotype distribution among IBD, Crohn's disease (CD), ulcerative colitis (UC) patients and healthy controls were compared. The frequency of the variant allele in healthy subjects was 1.77% compared to 2.56% in the IBD patients and 1.85% in CD patients. Furthermore, the frequency of this allele was increased in UC patients compared to controls (4.17% vs. 1.77%, OR = 2.42, 95% CI 0.82-7.08; P = 0.09), but the difference was not statistically significant. Our data suggest a lack of association between PTPN22 R620W variant and IBD susceptibility in Moroccan patients.

6.
BMC Med Genet ; 19(1): 127, 2018 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-30053839

RESUMO

BACKGROUND: Hypertension is a multifactorial disease involving both environmental and genetic Factros. G894 T eNOS polymorphism has been suggested to be responsible for reduced NO synthesis, and EH development. The objective of our case-control study is to evaluate the potential association of G894 T eNOS polymorphism with Essential Hypertension (EH) susceptibility, among a sample of Moroccan patients. METHODS: One hundred forty five hypertensive patients were recruited from the department of Cardiology, University Hospital Center Ibn Rochd, Casablanca, Morocco, and compared to 184 apparently healthy subjects. DNA samples were genotype by PCR-RFLP method using MboI restriction enzyme. RESULTS: Our results showed a positive correlation between G894 T eNOS distribution and Alcohol and Obesity rik factors (P = 0.009 and 0.02 respectively). Patients with elevated Cardio Vascular Risk (CVR) carried out the higher frequency of homozygous mutant genotype TT (62.2%) and T mutant allele (77.8%), compared to median and low CVR groups. G894 T eNOS distribution was significantly associated to a high risk of EH occurrence under the GT and TT genotypes (OR [95% CI] = 20.2 [7.7-52.4], P < 0.0001; OR [95% CI] = 332.5 [98.2-1125.4], P < 0.0001 respectively), and the 3 genotypic transmission models (Dominant: OR [95% CI] = 43.2 [17.9-104.09], P < 0.0001; Recessive: OR [95% CI] = 47.7 [18.6-122.3]; P < 0.0001; Additive: OR [95% CI] = 14.02 [9.6-20.45], P < 0.0001). CONCLUSION: Our study suggests a strong association of G894 T eNOS polymorphism with susceptibility to EH in Morocco. Studies trying to identify contributing genes may be very useful and allow recognizing the vulnerable individuals and classifying patients in subgroups with definite genetic and pathogenic mechanisms to achieve better prevention and therapeutics.

7.
Pathobiology ; 85(4): 247-253, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29949804

RESUMO

BACKGROUND: The purpose of our case control study is to explore the potential association of tumor protein 53 (TP53) c.215G>C, p. (Arg72Pro) polymorphism (rs1042522) with the risk of breast cancer (BC) development in the Moroccan population. METHODS AND RESULTS: The study population consisted of 125 female patients with confirmed BC and 126 healthy controls. DNA samples were genotyped by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism assay method using BstUI restriction enzyme. We showed that the homozygous genotype of TP53 72Pro variant was significantly associated with increased BC risk (OR 2.2, 95% CI 1.07-4.54, p = 0.03). The dominant and additive models of TP53 Pro allele were also correlated to the risk of BC (OR 2.13, 95% CI 1.07-4.23, p = 0.02 and OR 1.49, 95% CI 1.03-2.16, p = 0.03, respectively). Furthermore, the TP53 Arg72 variant was associated with protection against BC, either in the homozygous genotype, the dominant or the additive models (OR 0.45, 95% CI 0.22-0.93, p = 0.03; OR 0.46, 95% CI 0.23-0.92, p = 0.029 and OR 0.67, 95% CI 0.46-0.97, p = 0.03, respectively). CONCLUSION: Our results suggest that TP53 c.215G>C, p. (Arg72Pro) polymorphism may be considered as a genetic marker for predisposition to BC in Moroccan population.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Predisposição Genética para Doença/genética , Proteína Supressora de Tumor p53/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Marrocos , Polimorfismo de Nucleotídeo Único , Adulto Jovem
8.
BMC Res Notes ; 11(1): 46, 2018 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-29347970

RESUMO

OBJECTIVE: The main objective of our study was to investigate the association of CYP2C19*2 and CYP2C19*3 loss-of-function and CYP2C19*17 gain-of-function variants of CYP2C19 gene with Clopidogrel resistance in a sample of Moroccan Acute Coronary Syndromes patients. RESULTS: Our results showed the existence of a synergic effect between the three alleles, statistically very significant, on Clopidogrel resistance among the treated patients (P = 0.0033). For the three variants of the CYP2C19 gene, the heterozygous and homozygous mutant genotypes were the most frequent among ACS patients (CYP2C19*2: 82.76% GA and 10.35% AA; CYP2C19*3: 76.67% GA and 18.33% AA; CYP2C19*17: 66.67% CT and 18.66% TT). Allelic frequencies were 51.73% vs 48.27% (P < 0.001); 56.67% vs 43.33% (P < 0.001); and 52% vs 48% (P = 0.01) for the mutant and wild type alleles of the CYP2C19*2, CYP2C19*3 and CYP2C19*17 variants respectively. Our results support a role of CYP2C19 gene variants as a potential marker of Clopidogrel response. Understanding the functional and clinical consequences of these variants may help for treating patients more effectively, they could be genetically screened and appropriate dose adjustments could be made on the basis of their CYP2C19 genotype.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Citocromo P-450 CYP2C19/genética , Resistência a Medicamentos/genética , Variação Genética , Ticlopidina/análogos & derivados , Síndrome Coronariana Aguda/genética , Idoso , Alelos , Clopidogrel , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Marrocos , Inibidores da Agregação de Plaquetas/uso terapêutico , Ticlopidina/uso terapêutico
9.
Neuroscience ; 370: 181-190, 2018 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-28729061

RESUMO

The biomarkers may be useful for predictive diagnosis of Alzheimer's disease (AD). The current challenge is to diagnose it in its preclinical phase. The combination of cerebrospinal fluid (CSF) biomarkers and imaging has been investigated extensively for a number of years. It can provide an increased diagnostic accuracy. This review discusses the contribution of classical biomarkers to predict AD and highlights novel candidates identified as potential markers for AD. We referred to the electronic databases PubMed/Medline and Web of Science to search for articles that were published until February 2016. Sixty-two records were included in qualitative synthesis. In the first section, the results show the contribution of biomarkers to predict and track AD considered as classical biomarkers. In the second section, the results highlight the involvement of novel candidates that should be considered for future evaluation in the characterization of the AD progression. Reported findings open prospect to define noninvasive biomarkers to predict AD before symptoms onset.

10.
BMC Res Notes ; 10(1): 763, 2017 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-29268798

RESUMO

OBJECTIVE: Our case-control study aimed to access the potential association of insertion/deletion (I/D) ACE (angiotensin converting enzyme) gene polymorphism with myocardial infarction (MI) risk of occurrence among a sample of Moroccan patients, especially young ones. RESULTS: Distribution of I/D ACE gene variant among cases vs controls, showed that healthy controls carried out higher frequency of wild type allele I compared to cases (23.5% vs 21.79% respectively), when cases were carrying higher frequency of mutant allele D (78.21% vs 76.5% for controls). Patients were-after this- divided into two groups of < 45 and > 55 years of age, to investigate whether or not younger patients carried out higher frequency of the mutant allele D, than older ones. As expected, < 45 years old patients carried out more DD genotype than older ones (68.9% vs 54.6% respectively), and higher frequency of mutant allele D (81.08% vs 75% respectively). Besides, a tendency to a positive association was found under the recessive genetic transmission model (OR [95% CI] = 1.85 [0.93-3.69], P = 0.08), suggesting that the I/D ACE polymorphism may be associated with MI occurrence among younger patients (< 45 years of age).


Assuntos
Predisposição Genética para Doença/genética , Mutação INDEL , Infarto do Miocárdio/genética , Peptidil Dipeptidase A/genética , Polimorfismo Genético , Adulto , Alelos , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Marrocos , Infarto do Miocárdio/enzimologia , Fatores de Risco
11.
BMC Res Notes ; 10(1): 704, 2017 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-29208038

RESUMO

OBJECTIVE: Xeroderma pigmentosum (XP) is a genetically and clinically heterogeneous disease, associated with an inherited defect in one of eight different genes (XPA to XPG and XPV). In addition to the early onset of the skin manifestations, the XP group A is marked by the presence of a mild to severe neural disorders which appear tardily and worsens with age. In this study, 9 patients with moderate clinical profile belonging to 6 XP families were recruited to determine the XPA mutational spectrum in Morocco, using the direct sequencing of the whole coding region of the XPA gene. RESULTS: The genetic investigation of the XPA gene showed that 7 from 9 patients were homozygous for the c.682C>T, p.Arg228X mutation, while all their investigated family members were heterozygous. The frequency of this mutation was estimated to be 83.33% (5/6 families) .The molecular analysis of the 5 other exons of the XPA gene, showed that the 2 negative siblings carried no mutation in the XPA gene. This finding suggests that c.682C>T (p.Arg228X) mutation is relatively associated with moderate phenotype in XP group A Moroccan families; this result will also contribute to improve the molecular diagnosis of XP disease in Moroccan patients.


Assuntos
Mutação , Proteína de Xeroderma Pigmentoso Grupo A/genética , Xeroderma Pigmentoso/genética , Adolescente , Adulto , Criança , Feminino , Heterozigoto , Homozigoto , Humanos , Masculino , Marrocos , Linhagem , Fenótipo , Xeroderma Pigmentoso/patologia
12.
J Pediatr Genet ; 6(4): 205-214, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29142762

RESUMO

Primary congenital glaucoma (PCG) is the most common type of infantile glaucoma, yet it remains a relatively rare disease, because the disease is often transmitted in an autosomal recessive pattern. However, PCG occurs up to 10 times more frequently in certain ethnic and geographical groups where consanguineous relationships are common. The aim of this study was to investigate the distribution of mutations in the cytochrome P450 1B1 gene ( CYP1B1 ) in patients with PCG among different populations around the world from 2011 until May 2016. We referred to the electronic databases, such as Medline, Clinicalkey, Scopus, and ScienceDirect, to search for articles that were published in this area. Nineteen records were included in this qualitative synthesis. CYP1B1 mutations were assessed in 1,220 patients with PCG and identified in 41.6% of them. According to these studies, 99 mutations including 60 novel mutations were found. Nonsignificant difference in the sex ratio has been reported. This current review shows that consanguinity plays an important role in the PCG pathogenesis and transmission; however, sporadic mutations have been found in some cases. A difference in penetrance was highlighted by some mutations. The CYP1B1 mutations were mostly found in the Middle East and the Maghreb with a rate of 64.8 and 54.4%, respectively, followed by Europe (34.7%), Asia (21.3%), and finally the United States (14.9%). Founder mutations in different geographical areas have been discovered. For instance, the p.Gly61Glu, p.Arg390His, p.Gly61Glu, c.4,339delG, p.E387Lys, and p.Val320Leu were considered founder mutations for Iran/Saudi Arabia, Pakistan, Lebanon, Morocco, Europe, and Vietnam/South Korea, respectively. Many common mutations in different countries were found, such as in Morocco, where its mutations were similar to seven other countries. These findings suggest that the ethnic differences and the geographical distribution of PCG give us a large CYP1B1 mutation pattern. Genetic tests looking for founder and common mutations should be the first step in genetic screening for patients with PCG.

13.
Case Rep Dent ; 2017: 8302039, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29075537

RESUMO

The aim of this work is to present a case of management of an open apex on a lower molar by using tissue engineering, with two endodontic procedures in the same tooth. We had to resort to pulp regeneration on the distal root and apexification with MTA on the mesial roots after the failure of regenerative therapy on those ones. The management consisted in scheduling regular follow-ups combined with X-rays. After 24 months, the radiological control has shown pulpo-periodontal regeneration associated with walls thickening and distal root elongation and periapical ad integrum healing.

14.
Genet Res Int ; 2017: 9532471, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28261502

RESUMO

Background. An interindividual variability in response to Clopidogrel has been widely described in patients with acute coronary syndromes (ACS). The contribution of genetics on modulating this response was widely discussed. The objective of our study was to investigate the potential effect of i-T744C P2Y12 polymorphism on Clopidogrel response in a sample of Moroccan ACS patients. We tried also to determine the frequency of this polymorphism among Moroccan ACS compared to healthy subjects. Methods and Results. 77 ACS patients versus 101 healthy controls were recruited. DNA samples were genotyped by PCR-RFLP method. The VerifyNow assay was used to evaluate platelet function among ACS patients. Our results show that the mutant allele C was more frequent among ACS ST (+) than ST (-) patients (39% versus 19.8%, resp.), when the wild-type allele was more represented in the ACS ST (-) group (80.2%). The C allele frequency was higher among resistant than nonresistant patients (30% versus 20.8%, resp.). Comparison of ACS patients and healthy controls shows higher frequency of mutant C allele among cases compared to controls (22.73% versus 19.31%, resp.); there was a statistically significant association of the recessive and additive transmission models with the ACS development risk (OR [95% CI] = 1.78 [1.58-5.05], P = 0.01 and OR [95% CI] = 1.23 [0.74-2.03], P < 0.001, resp.), increasing thus the association of this polymorphism with the pathology. Conclusion. Our results suggest that this polymorphism may have a potential effect on Clopidogrel response among our Moroccan ACS patients and also on ACS development.

15.
BMC Complement Altern Med ; 17(1): 81, 2017 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-28143472

RESUMO

BACKGROUND: Several chronic inflammatory diseases are characterized by inappropriate CD4+ T cell response. In the present study, we assessed the ability of Capparis spinosa L. (CS) preparation to orientate, in vivo, the immune response mediated by CD4+ T cells towards an anti-inflammatory response. METHODS: The in vivo study was carried out by using the contact hypersensitivity (CHS) model in Swiss mice. Then we performed a histological analysis followed by molecular study by using real time RT-PCR. We also realized a phytochemical screening and a liquid-liquid separation of CS preparation. RESULTS: Our study allowed us to detect a significantly reduced edema in mice treated with CS preparations relative to control. CS effect was dose dependent, statistically similar to that observed with indomethacin, independent of the plant genotype and of the period of treatment. Furthermore, our histology studies revealed that CS induced a significant decrease in immune cell infiltration, in vasodilatation and in dermis thickness in the inflammatory site. Interestingly, we showed that CS operated by inhibiting cytokine gene expression including IFNγ, IL-17 and IL-4. Besides, phytochemical screening of CS extract showed the presence of several chemical families such as saponins, flavonoids and alkaloids. One (hexane fraction) out of the three distinct prepared fractions, exhibited an anti-inflammatory effect similar to that of the raw preparation, and would likely contain the bioactive(s) molecule(s). CONCLUSIONS: Altogether, our data indicate that CS regulates inflammation induced in vivo in mice and thus could be a source of anti-inflammatory molecules, which could be used in some T lymphocyte-dependent inflammatory diseases.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Capparis/química , Citocinas/genética , Extratos Vegetais/farmacologia , Acetatos , Animais , Anti-Inflamatórios não Esteroides/isolamento & purificação , Capparis/genética , Dermatite de Contato/tratamento farmacológico , Dermatite de Contato/etiologia , Dinitrofluorbenzeno , Feminino , Expressão Gênica/efeitos dos fármacos , Genótipo , Hexanos , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/patologia , Metanol , Camundongos
16.
J Clin Neurosci ; 40: 24-26, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28087189

RESUMO

INTRODUCTION: Neuroproteomics studies have showed the high affinity interactions between GAPDH - ß-amyloid in Alzheimer disease. The aim of our study is to complete our previous studies by assessing the mechanism responsible of decreased expression of GAPDH protein in the blood of Moroccan AD cases probably due to an alteration at the transcriptional level or at the post translational level. METHODS: The mRNA expression of GAPDH was assessed by quantitative real time PCR in AD cases and healthy controls. RESULTS: Our result revealed a significant difference of mRNA expression level of GAPDH in AD cases as compared to healthy controls (P<0.05). CONCLUSION: This data is consistent with several studies by showing the direct involvement of GAPDH in amyloid aggregation by undergoing several modifications, which influence its chemical structure and its biological activity.


Assuntos
Doença de Alzheimer/sangue , Gliceraldeído-3-Fosfato Desidrogenases/genética , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Gliceraldeído-3-Fosfato Desidrogenases/metabolismo , Humanos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
17.
Forensic Sci Int Genet ; 27: 167-171, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27931869

RESUMO

The forensic use of X-STRs requires the creation of allele and haplotype frequency databases in the populations where they are going to be used. Recently, an updated Spanish allele and haplotype frequency database for the new 17 X-STR panel has been created, being the only database available up to now for this new multiplex. In order to broaden the forensic applicability of the 17 X-STR panel, 513 individuals from four different populations located on the Atlantic Coast of Europe and North-West Africa have been studied, i.e. Brittany (France), Ireland, northern Portugal, and Casablanca (Morocco). Allele and haplotype frequency databases, as well as parameters of forensic interest for these populations are presented. The obtained results showed that the 17 X-STR panel constitutes a highly discriminative tool for forensic identification and kinship testing in the studied populations. Furthermore, we aimed to study if these populations located on the Atlantic coast actually share alike allele and haplotype frequency distributions since they have experienced genetic exchanges throughout history. This would allow creating larger forensic databases that include several genetically similar populations for its use in forensic casework. For this purpose, pairwise FST genetic distances between the analyzed populations and others from the Atlantic Coast previously studied with the 17 X-STR panel or the ten coincident markers included in the decaplex of the GHEP-ISFG were estimated. Our results suggest that certain nearby populations located on the European Atlantic coast could have underwent episodes of genetic interchange as they have not shown statistically significant differentiation between them. However, the population of Casablanca showed significant differentiation with the majority of the European populations. Likewise, the autochthonous Basque Country and Brittany populations have shown distinctive allele frequency distributions between them. Therefore, these findings seem to support that the use of independent allele and haplotype frequency databases for each population instead of a global database would be more appropriate for forensic purposes.


Assuntos
Cromossomos Humanos Y , Genética Populacional , Repetições de Microssatélites , Impressões Digitais de DNA , Europa (Continente) , Feminino , Frequência do Gene , Variação Genética , Haplótipos , Humanos , Masculino , Marrocos
18.
J Med Virol ; 89(4): 647-652, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27458866

RESUMO

Host genetic factors may influence the establishment of chronicity or spontaneous clearance in viral hepatitis B and C infections. More light was shed on the role played by interferon-stimulated genes in the innate immunity. Myxovirus resistance 1 (MX1) is one of those key genes that have reported to inhibit several viruses. The present study aims to explore the possible association of -88G/T and -123C/A promoter variants of MX1 with susceptibility to chronic hepatitis B and C and/or with spontaneous clearance in a Moroccan population. The -88G/T and -123C/A SNPs were genotyped by PCR-RFLP in 538 individuals stratified into HBV chronically infected patients (n = 120), HCV-chronically infected patients (n = 115), HBV spontaneously resolved subjects (n = 114), HCV spontaneously resolved group (n = 52), and healthy controls (n = 137). A significant association of -123C allele with HBV spontaneous clearance has been found (P = 0.002, OR = 2.34; 95%CI [1.36-4]). In addition, a significant correlation between the MX1-GC haplotype and HBV spontaneous clearance (P < 0.001) was found. No significant association of -88G/T and -123C/A polymorphisms with regard to HCV infection was observed in this study. Here, we show that for North African patients with chronic hepatitis, MX1 gene variation at position -123 may influence the outcome of HBV infection but not HCV infection. J. Med. Virol. 89:647-652, 2017. © 2016 Wiley Periodicals, Inc.


Assuntos
Predisposição Genética para Doença , Hepatite B Crônica/genética , Hepatite C Crônica/genética , Proteínas de Resistência a Myxovirus/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Feminino , Técnicas de Genotipagem , Humanos , Masculino , Pessoa de Meia-Idade , Marrocos , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Regiões Promotoras Genéticas , Adulto Jovem
19.
Mol Neurobiol ; 54(2): 939-942, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-26790671

RESUMO

Myoclonus-dystonia (M-D) is an autosomal-dominant movement disorder with onset in the first two decades of life. Mutations in the epsilon-sarcoglycan gene (SGCE, DYT11) on chromosome 7q21-q31 represent the major genetic cause of M-D in some populations. The syndrome was related with mutations in two other genes (DRD2 and DYT1). A second locus has been reported in one large M-D family (DYT15, 18p11), but no gene has been identified yet. In this review, we discuss genetic aspects of myoclonus-dystonia.


Assuntos
Distúrbios Distônicos/genética , Predisposição Genética para Doença/genética , Mutação/genética , Animais , Distonia Muscular Deformante/diagnóstico , Distonia Muscular Deformante/epidemiologia , Distonia Muscular Deformante/genética , Distúrbios Distônicos/diagnóstico , Distúrbios Distônicos/epidemiologia , Predisposição Genética para Doença/epidemiologia , Humanos , Sarcoglicanas/genética
20.
J Gastroenterol Hepatol ; 32(6): 1212-1220, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27869326

RESUMO

BACKGROUND: Inflammatory bowel diseases (IBD) are chronic multi-factorial inflammatory disorders. Accumulating investigations have provided compelling evidence that describe the interplay of a complex genetic landscape and inappropriate inflammatory response to intestinal microbes in disease etiopathogenesis but still pose challenges in diagnostic practices. METHOD: In this study, comparative proteomic analysis was conducted to identify disease specific proteins underlying IBD pathogenetic mechanisms. Total blood proteins of the IBD patients and healthy subjects were analyzed with one-dimensional electrophoresis; differentially expressed bands were excised and subjected to matrix-assisted laser desorption ionization-time of flight mass spectrometry along with nanoflow liquid chromatography electrospray ionization-tandem mass spectrometry analysis. Presence of glycosylation, hydroxylation, and phosphorylation post-translational modifications was further investigated by immunoprecipitation. RESULTS: Peroxiredoxin-2 (PRDX2) and hemoglobin-subunits proteins, which are closely involved in the response to oxidative stress, were identified. PRDX2 was selected for further validation using western blot and reverse transcription-polymerase chain reaction. PRDX2 overexpression was restricted to the protein level within the membrane fraction. Immunoprecipitation identified PRDX2 to be post-translationally glycosylated and phosphorylated. CONCLUSION: Our findings demonstrate the implication of PRDX2 in IBD. Future studies are required to establish its functional role and to determine the clinical utility.


Assuntos
Expressão Gênica , Doenças Inflamatórias Intestinais/genética , Peroxirredoxinas/genética , Peroxirredoxinas/metabolismo , Regulação para Cima , Adulto , Feminino , Glicosilação , Humanos , Hidroxilação , Masculino , Estresse Oxidativo/genética , Fosforilação
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