RESUMO
La diabetes tipo MODY se produce por alteraciones en genes relacionados con el metabolismo de la célula beta pancreática. El tipo 2 es uno de los más frecuentes y se produce por alteraciones en el gen GCK (glucoquinasa) y el tipo 5 es mucho menos frecuente y se produce por alteraciones en el gen HNF1B (factor nuclear hepático 1B). Se presentan con herencia autosómica dominante, aunque se ha descripto la presencia de mutaciones de novo. El objetivo del trabajo fue buscar mutaciones en el gen GCK en pacientes sin antecedentes familiares pero con características clínicas de MODY2 y mutaciones en el gen HNF1B en pacientes con características clínicas de MODY5 con y sin antecedentes familiares. Para ello a partir de ADN se realizó la secuenciación de cada gen por el método de Sanger o por secuenciación de nueva generación. Como resultado, se hallaron mutaciones en el gen GCK en cuatro pacientes sin antecedentes familiares y mutaciones en el gen del HNF1B en dos pacientes, uno de ellos sin antecedentes familiares. Como conclusión puede afirmarse que las mutaciones de novo en el gen de la GCK son más frecuentes de lo descripto, por lo cual se recomienda el estudio del gen en pacientes con características compatibles aún sin antecedentes familiares. También es importante el estudio del gen HNF1B en pacientes con características típicas ya que deben tratarse no sólo por sus alteraciones renales sino por la diabetes presente; de esta manera se logra un correcto diagnóstico para instaurar el tratamiento más adecuado
Assuntos
Diabetes Mellitus Tipo 2 , Fator 1-beta Nuclear de Hepatócito , GlucoquinaseRESUMO
OBJECTIVES: The aim of the study was to understand which human papillomavirus (HPV) types are involved in external genital warts (GWs) in a group of Argentinian women in Buenos Aires. METHODS: One hundred sixty consecutive women 15 to 45 years old with GWs were enrolled. All patients underwent confirmatory biopsy. In 150 of 160 patients, the diagnosis of GWs was confirmed by histology, DNA-HPV was investigated using polymerase chain reaction, and sequence analysis with generic primers MY09/11 was performed. RESULTS: HPV 6 and/or 11 was detected in 93.3% patients (140/150). HPV 6 was by far the most common type (80%), followed by HPV 11 (12.7%). Coinfection with these 2 types occurred in 0.7%. HPV 16 was found in 2% and HPV 73 in 0.7%. CONCLUSION: HPV 6 and/or 11 are present in 93.3% (95% confidence interval, 0.9-1.0) of external genital warts in a group of Argentinian women in Buenos Aires and, therefore, could be prevented with HPV vaccine (NCT 015998779).
Assuntos
Condiloma Acuminado/epidemiologia , Condiloma Acuminado/virologia , Genótipo , Papillomaviridae/classificação , Papillomaviridae/isolamento & purificação , Adolescente , Adulto , Argentina/epidemiologia , Biópsia , DNA Viral/genética , DNA Viral/isolamento & purificação , Feminino , Histocitoquímica , Humanos , Pessoa de Meia-Idade , Papillomaviridae/genética , Reação em Cadeia da Polimerase , Prevalência , Análise de Sequência de DNA , Adulto JovemRESUMO
BACKGROUND: Maturity-onset diabetes of the young 2 (MODY2) is a form of diabetes that is clinically characterized by early age at onset and mild hyperglycemia, and has a low risk of late complications. It is often underdiagnosed due to its mild symptoms. To date, over 600 different GCK/MODY2 mutations have been reported. Despite only a few de novo mutations having been described, recent studies have reported the detection of a higher frequency of this kind of mutation. Therefore, de novo mutations could be more frequent than previously described. Even though common recommendations regarding the diagnosis of monogenic diabetes include the existence of a strong family history of diabetes, here we describe the study of mutations in two families with a symptomatic individual with clear clinical features of MODY2 but without any family history of diabetes. METHODS: Genetic diagnosis in a group of participants with MODY2 characteristics was carried out by direct sequencing of coding regions of the GCK gene and analysis of mutations found using bioinformatics tools. RESULTS: We found two de novo mutations, one of them novel, constituting 14.29% of all the participants who were phenotyped as MODY2. CONCLUSIONS: The number of mutations in GCK/MODY2 or even other MODY-related genes is undoubtedly underestimated, as accepted criteria for performing genetic tests include family history of the pathology. These cases illustrate the value of analyzing the GCK gene in patients with clinical features of MODY2, even in the absence of family history of the condition as it is essential for establishing the correct treatment.
Assuntos
DNA/genética , Diabetes Mellitus Tipo 2/genética , Glucoquinase/genética , Mutação , Adolescente , Argentina/epidemiologia , Análise Mutacional de DNA/métodos , Diabetes Mellitus Tipo 2/enzimologia , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Glucoquinase/metabolismo , Humanos , Masculino , Linhagem , Fenótipo , Prevalência , Estudos RetrospectivosRESUMO
In the present study, the molecular characterization of HPV variants 16, 18, 31, 58, 6 and 11 within the MY06/MY11 L1 genomic region was performed in 128 sequences. For HPV 16, all of the sequences analyzed had a 3 nucleotide insertion resulting in the insertion of serine in the L1 protein sequence; and 4 sequences had at least one single nucleotide polymorphism (SNP). Twelve base substitutions were detected in HPV 58, 6 SNPs produced amino acid changes, and the other SNPs detected were found to be silent mutations. For HPV 31, 25 SNPs were detected as silent mutations. Of the 8 SNPs detected on HPV 18, three produced amino acid changes, the remaining SNPs detected were silent mutations. For HPV 6, 10 SNPs were detected and none of them produced amino acid changes. From the 16 sequences analyzed for HPV 11, two SNPs were detected and neither of them produced amino acid substitutions. Phylogenetic trees were constructed for HPV 16, HPV 18, HPV 31, HPV 58, HPV 6 and HPV 11. In the current study 8 new variants were identified based on sequencing of the L1 region. Changes in the L1 region of the HPV genome may be important for discriminating the infectious potential of different variants, as well as in defining epitopes relevant to vaccine design. The findings of this study indicate that there are new variants of HPV circulating in Argentina, which need to be confirmed by further analyses of the complete HPV genome.
RESUMO
Inicialmente el virus de influenza A(H1N1)pdm09 fue susceptible a los inhibidores de neuraminidasa oseltamivir y zanamivir. Las cepas virales resistentes presentan una sustitución que produce un cambio del aminoácido histidina (H) por una tirosina (Y) en el codón 274 del gen de la neuroaminidasa. El objetivo del trabajo fue realizar un análisis retrospectivo de los resultados obtenidos en muestras estudiadas para influenza A durante el periodo junio - agosto de 2013 y en las muestras positivas determinar la presencia de la mutación H274Y. Se estudiaron 1783 muestras de pacientes con diagnóstico presuntivo de influenza A(H1N1)pdm09, 171 (9.6%) resultaron positivas, a estas se les estudió la presencia de la mutación H274Y. Únicamente dos muestras presentaron la mutación de resistencia. Los métodos para detectar cepas de infuenza A(H1N1)pdm09 resistentes son necesarios para ayudar a los médicos en la selección de la terapia antiviral apropiada de la influenza.
Initially the circulating influenza virus A(H1N1)pdm09 was susceptible to neuraminidase inhibitors oseltamivir and zanamivir. Virtually all resistant viruses possess a substitution at codon 274 of the neuraminidase gene which produces a change of the amino acid histidine (H) to a tyrosine (Y). The aims of the study were to perform a retrospective analysis of samples studied in the Laboratory of Genomic Medicine - MANLAB for influenza A during the period June to August 2013 in Buenos Aires, and to determine the presence of the H274Y mutation. 1783 samples from patients with a presumptive diagnosis of influenza A(H1N1) pdm09 were studied, the virus was detected in 171 samples (9.6%). Then, we studied the presence of the mutation H274Y. Only two samples showed the characteristic resistance mutation. Methods for detecting oseltamivir-resistant A(H1N1)pdm09 influenza strains are needed to assist physicians in the selection of appropriate antiviral therapy for influenza treatment.
Assuntos
Vírus da Influenza A , Vírus da Influenza A Subtipo H1N1 , OseltamivirRESUMO
Mundialmente se han identificado 6 genotipos (1 al 6) del virus de la hepatitis C (HCV). Dichos genotipos se subdividen en diferentes subtipos (a, b, c y otros). La respuesta al tratamiento instaurado depende del genotipo del virus infectante. El objetivo del trabajo fue determinar la frecuencia de los diferentes genotipos del HCV en la población de Argentina. Se estudiaron 510 pacientes infectados con HCV; la genotipificación del virus se realizó utilizando el equipo Versant HCV genotype assay 2.0 (LiPA). Los resultados obtenidos indican que el genotipo predominante del HCV en Argentina es el 1 (67,6%), con una prevalencia similar de subtipos 1a y 1b (33,3% y 34,5%, respectivamente). Se observó también una frecuencia similar de los genotipos 2 y 3 (14,5% cada uno). Con este estudio se actualizan los datos de las frecuencias de los diferentes genotipos de HCV que circulan en Argentina utilizando la nueva versión del reactivo para diagnóstico, el cual permitió una correcta subtipificación de las muestras.
Six hepatitis C virus genotypes have been identified worldwide so far. These genotypes have been subclassified into different subtypes (a, b, c and others). It is known that the response to treatment is highly dependent on the genotype involved. The aim of this work was to assess the frequency of occurrence of the different HCV genotypes in the population of Argentina. To this end, 510 infected patients were subjected to HCV genotyping using the commercial kit Versant HCV genotype assay 2.0. Results indicated that the genotype 1 was the most frequent (67.6%), and that subtypes 1a and 1b showed a similar prevalence (33.3% and 34.5%, respectively). Genotypes 2 and 3 also displayed a similar frequency (14.5% and 14.5% respectively). This study provides an update regarding the frequency of all HCV genotypes circulating in Argentina. The results were obtained by the novel version of the genotyping kit, which enabled a correct subtyping of samples.
Globalmente foram identificados 6 genótipos (1 ao 6) do vírus da hepatite C (HCV). Estes genótipos são subdivididos em vários subtipos (a, b, c, etc.). A resposta ao tratamento depende do genótipo do vírus infectante. O objetivo do estudo foi determinar a freqüência dos diferentes genótipos do HCV na população Argentina. Foram estudados 510 pacientes infectados com o HCV, a genotipagem do vírus foi realizada utilizando o kit Versant HCV genotype assay 2.0 (LiPA). Os resultados obtidos indicam que o genótipo predominante na Argentina é o tipo 1 (67,6%), observando-se uma prevalência dos subtipos 1a e 1b (33,3% e 34,5% respectivamente). Observou-se também uma freqüência semelhante do genótipos 2 e 3 (14,5% e 14,5% respectivamente). Este estudo atualiza os dados das freqüências dos diferentes genótipos do HCV em circulação na Argentina usando a nova versão do kit, o que permitiu uma correta subtipagem das amostras.
Assuntos
Humanos , Hepacivirus/genética , Hepatite C/sangue , Argentina , Genótipo , Hepatite C , Hepatite C/urinaRESUMO
Mundialmente se han identificado 6 genotipos (1 al 6) del virus de la hepa¡titis C (HCV). Dichos genotipos se subdividen en diferentes subtipos (a, b, c y otros). La respuesta al tratamiento instaurado depende del genotipo del virus infectante. El objetivo del trabajo fue determinar la frecuencia de los diferentes genotipos del HCV en la población de Argentina. Se estudiaron 510 pacientes infectados con HCV; la genotipificación del virus se realizó utilizando el equipo Versant HCV genotype assay 2.0 (LiPA). Los resultados obtenidos indican que el genotipo predominante del HCV en Argentina es el 1 (67,6%), con una prevalencia similar de subtipos 1a y 1b (33,3% y 34,5%, respectivamente). Se observó también una frecuencia similar de los genotipos 2 y 3 (14,5% cada uno). Con este estudio se actualizan los datos de las frecuencias de los diferentes genotipos de HCV que circulan en Argentina utilizando la nueva versión del reactivo para diagnóstico, el cual permitió una correcta subtipificación de las muestras.(AU)
Six hepatitis C virus genotypes have been identified worldwide so far. The¡se genotypes have been subclassified into different subtypes (a, b, c and others). It is known that the response to treatment is highly dependent on the genotype involved. The aim of this work was to assess the frequency of occurrence of the different HCV genotypes in the population of Argentina. To this end, 510 infected patients were subjected to HCV genotyping using the commercial kit Versant HCV genotype assay 2.0. Results indicated that the genotype 1 was the most frequent (67.6%), and that subtypes 1a and 1b showed a similar prevalence (33.3% and 34.5%, respectively). Genotypes 2 and 3 also displayed a similar frequency (14.5% and 14.5% respectively). This study provides an update regarding the frequency of all HCV genotypes circulating in Argentina. The results were obtained by the novel version of the genotyping kit, which enabled a correct subtyping of samples.(AU)
Globalmente foram identificados 6 genótipos (1 ao 6) do vírus da hepatite C (HCV). Estes genótipos sÒo subdivididos em vários subtipos (a, b, c, etc.). A resposta ao tratamento depende do genótipo do vírus infectante. O objetivo do estudo foi determinar a freq³Ûncia dos diferentes genótipos do HCV na populaþÒo Argentina. Foram estudados 510 pacientes infectados com o HCV, a genotipagem do vírus foi realizada utilizando o kit Versant HCV genotype assay 2.0 (LiPA). Os resultados obtidos indicam que o genótipo predominante na Argentina é o tipo 1 (67,6%), observando-se uma prevalÛncia dos subtipos 1a e 1b (33,3% e 34,5% respectivamente). Observou-se também uma freq³Ûncia semelhante do genótipos 2 e 3 (14,5% e 14,5% respectivamente). Este estudo atualiza os dados das freq³Ûncias dos diferentes genótipos do HCV em circulaþÒo na Argentina usando a nova versÒo do kit, o que permitiu uma correta subtipagem das amostras.(AU)
RESUMO
AIMS: To explore associations between IRS-1 rs1801278 G>A polymorphism and metabolic syndrome (MS). METHODS: rs1801278 G>A was genotyped in 610 healthy Argentinian men. RESULTS: GA carriers had lower risk of MS (OR=0.52, P=0.045), particularly among smokers (OR=0.10, P=0.006). CONCLUSIONS: rs1801278 GA carriers had lower risk of MS, especially among smokers.
Assuntos
Proteínas Substratos do Receptor de Insulina/genética , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/genética , Polimorfismo Genético/genética , Fumar/efeitos adversos , Adolescente , Adulto , Idoso , Argentina/epidemiologia , Genótipo , Humanos , Resistência à Insulina/genética , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto JovemRESUMO
INTRODUCTION: There are at least six subtypes of Maturity Onset Diabetes of the Young (MODY) with distinctive genetic causes. MODY 3 is caused by mutations in HNF1A gene, an insulin transcription factor, so mutations in this gene are associated with impaired insulin secretion. MODY 3 prevalence differs according to the population analyzed, but it is one of the most frequent subtypes. Therefore, our aims in this work were to find mutations present in the HNF1A gene and provide information on their prevalence. MATERIAL AND METHODS: Mutations screening was done in a group of 80 unrelated patients (average age 17.1 years) selected by clinical characterization of MODY, by SSCP electrophoresis followed by sequenciation. RESULTS: We found eight mutations, of which six were novel and four sequence variants, which were all novel. Therefore the prevalence of MODY 3 in this group was 10%. Compared clinical data between the non-MODY 3 patients and the MODY 3 diagnosed patients did not show any significant difference. DISCUSSION: Eight patients were diagnosed as MODY 3 and new data about the prevalence of that subtype is provided. Our results contribute to reveal novel mutations, providing new data about the prevalence of that subtype.
Assuntos
Diabetes Mellitus Tipo 2/genética , Fator 1-alfa Nuclear de Hepatócito/genética , Adolescente , Adulto , Argentina , Criança , Pré-Escolar , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Mutação , População Branca , Adulto JovemRESUMO
BACKGROUND: The Pro12Ala polymorphism (rs1801282), a nonsynonymous substitution of peroxisome proliferator-activated receptor-gamma (PPARG), has been robustly associated with type 2 diabetes. However, its role in metabolic syndrome (MetS) remains poorly understood. The associations among rs1801282, MetS and surrogate measures of insulin resistance (IR) were investigated in the present study. METHODS AND RESULTS: A cross-sectional population-based survey of 572 unrelated healthy male Argentinian blood donors with normal findings on medical examination and not taking any medication was conducted. MetS was assessed using the National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATP III) criteria, and the HOMA-IR, and QUICKI were calculated. Genotyping of rs1801282 was performed using RFLP-PCR. The prevalence of MetS was 26.2%. The Pro/Ala genotype (and the Ala12 allele) was associated with a high risk for MetS (odds ratio (OR) 1.67 [95% confidence interval (CI) 1.03-2.72], P=0.0394). This was highlighted among nonsmokers (OR 2.20 [95%CI 1.25-3.88], P=0.0059). ANCOVA confirmed an interaction between smoking status and this association (P=0.031). Ala12 carriers had a higher waist circumference than noncarriers (P=0.0065). Among nonsmokers, surrogates of IR, such as HOMA-IR, were significantly higher in Ala12 carriers than in noncarriers (P<0.05). CONCLUSIONS: Healthy men, in particular nonsmokers, carrying the Ala12 allele of PPARG rs1801282 polymorphism, have a high risk for MetS and IR.