Association between alpha 1 antitrypsin deficiency and cystic fibrosis severity

OBJECTIVE: To ascertain the distribution of alpha 1 antitrypsin genotypes and correlate it with the severity of pulmonary disease in patients with cystic fibrosis METHOD: A clinical and laboratory cross sectional study of 70 patients at the Universidade Estadual de Campinas teaching hospital. Cystic fibrosis diagnoses was confirmed by both clinical and laboratory methods. The severity of cystic fibrosis was evaluated by Shwachman score. All the patients were tested for the presence of S and Z alleles for alpha 1 antitrypsin deficiency using polymerase chain reaction. RESULTS: Nine (12.8%) patients were heterozygous for S or Z alleles or the heterozygote compound (SZ). No significant differences were found in clinical severity of Cystic fibrosis between genotypes of alpha 1 antitrypsin. No significant differences were found when the patients were divided according to the presence or absence of the deltaF508 mutation. CONCLUSION: In this study, the first undertaken in Brazil into the association of alpha 1 antitrypsin deficiency and cystic fibrosis, we did not find an association between the deficiency and cystic fibrosis severity.OBJETIVO: Verificar a distribuição dos genótipos da alfa-1-antitripsina e correlacionar com a gravidade da doença pulmonar em pacientes fibrocísticos. MÉTODO: Estudo clínico-laboratorial de corte transversal, com 70 pacientes fibrocísticos do Hospital Universitário da UNICAMP. Os fibrocísticos tiveram diagnóstico confirmado clínica e laboratorialmente. A gravidade da fibrose cística foi avaliada pelo escore de Shwachman. Todos os pacientes foram analisados para os alelos S e Z de alfa-1-antitripsina usando a reação em cadeia da polimerase. RESULTADOS: Nove pacientes (12,8%) foram heterozigotos para os alelos S ou Z ou heterozigoto composto (SZ). Nenhuma diferença significativa foi encontrada na gravidade clínica da fibrose cística entre os genótipos da alfa-1-antitripsina. Nenhuma diferença com significância estatística foi encontrada quando os pacientes foram separados pela presença ou ausência da mutação deltaF508. CONCLUSÃO: Neste estudo, o primeiro realizado no Brasil sobre a associação entre deficiência de alfa-1-antitripsina e fibrose cística, não encontramos uma associação entre essa deficiência e a gravidade da fibrose cística.485490Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Glutathione S-transferase mu 1 (GSTM1) and theta 1 (GSTT1) genetic polymorphisms and atopic asthma in children from Southeastern Brazil

Xenobiotics can trigger degranulation of eosinophils and mast cells. In this process, the cells release several substances leading to bronchial hyperactivity, the main feature of atopic asthma (AA). GSTM1 and GSTT1 genes encode enzymes involved in the inactivation of these compounds. Both genes are polymorphic in humans and have a null variant genotype in which both the gene and corresponding enzyme are absent. An increased risk for disease in individuals with the null GST genotypes is therefore, but this issue is controversial. The aim of this study was to investigate the influence of the GSTM1 and GSTT1 genotypes on the occurrence of AA, as well as on its clinical manifestations. Genomic DNA from 86 patients and 258 controls was analyzed by polymerase chain reaction. The frequency of the GSTM1 null genotype in patients was higher than that found in controls (60.5% versus 40.3%, p = 0.002). In individuals with the GSTM1 null genotype the risk of manifested AA was 2.3-fold higher (95%CI: 1.4-3.7) than for others. In contrast, similar frequencies of GSTT1 null and combined GSTM1 plus GSTT1 null genotypes were seen in both groups. No differences in genotype frequencies were perceived in patients stratified by age, gender, ethnic origin, and severity of the disease. These results suggest that the inherited absence of the GSTM1 metabolic pathway may alter the risk of AA in southeastern Brazilian children, although this must be confirmed by further studies with a larger cohort of patients and age-matched controls from the distinct regions of the country

Associação entre a presença dos alelos S e Z do gene da alfa 1 antitripsina com a gravidade da asma atopica na região de Campinas

Orientador : Carmen Silvia BertuzzoDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias MedicasResumo: A alfa 1 antitripsina (AIAT) é uma glicoproteína que inibe as proteases que desencadeiam as reações inflamatórias do plasma. Seu papel inibitório mais importante é o que realiza contra a elastase leucocitária, uma protease que degrada a elastina das paredes alveolares. É uma enzima polimórfica e várias variantes já foram descritas. Entre as variantes deficientes as mais importantes são os alelos S e Z. Em um estudo realizado na população do Estado de São Paulo, o alelo S alcançou a freqüência de 0,05, enquanto o alelo Z de 0,03. A deficiência de alfa 1 antitripsina (AIAT) tem sido associada com DPOC. A asma é uma doença crônica das vias aéreas caracterizada por uma obstrução do fluxo aéreo e hiperresponsividade brônquica. A asma, quanto a gravidade, é classificada em leve, moderada e grave. Este estudo teve como propósito a determinação da prevalência dos alelos S e Z do gene da AIAT, em escolares e adolescentes com asma atópica leve (Grupo 1), moderada (Grupo 2) e grave (Grupo 3) e verificar a presença de associação entre os alelos e variáveis clínicas nos diferentes grupos propostos. Foram analisados 93 pacientes do Ambulatório de Imunologia, Alergia e Pneumologia do Departamento de Pediatria da FCM- UNICAMP. A detecção dos alelos S e Z do gene da AIAT foi realizada pela reação em cadeia da polimerase (PCR) associada à digestão enzimática com as enzimas TaqI e XmnI. Dos 93 pacientes asmáticos analisados, 40 apresentavam a forma grave, 23 a moderada e 30 a leve. Ao se comparar com a prevalência desses alelos em nossa região, verifica-se uma prevalência maior dos alelos S e Z. Quando se separa por gravidade, verifica-se que o alelo Z é importante na manifestação da forma grave da doença. Por meio da análise dos resultados obtidos nesse estudo pode-se sugerir que os alelos S e Z são um fator de risco adicional para o desenvolvimento da asma e que esses alelos poderiam modular a gravidade da asmaAbstract: Alpha-1-antitrypsin (AIAT) is a glycoprotein that inhibits the proteases that release inflammatory plasmatic reactions. Its most important inhibitory effect is against leukocytic elastase, a protease that degrades elastin in the alveolar walls. It is a polymorphic enzyme and has various variants that have been described. The most important deficient variants are the S and Z alleles. In Brazil, the S allele attains a frequency of 0.05 , while the Z allele a frequency is of 0.03. Alpha-1-antitrypsin (AIAT) deficiency has been associated with DPOC. Asthma is a chronic disease of the airways that is characterized by air flow obstruction and bronchial hyper-responsiveness. Acording the severity, asthma is classified as light, moderate and severe. This study was undertaken to determine the prevalence of S and Z aneles in the AIAT gene of school students and adolescents with light (Groupl), moderate (Group 2) and severe (Group 3) atopic asthma and to verify the presence of a relationship between the alleles present in these groups and the clinical variables. The study sample consisted of93 asthmatic patients ftom the Immunology, Anergy and Pneumology Ambulatory Sector of the Department of Pediatrics , FCM-UNICAMP. The polymerase cOOinreaction (PCR) and the enzymatic digestion with TaqI and XmnI enzymes were used for detecting the AIAT gene S and Z aneles. These 93 asthmatic patients were c1assified as: severe -40 patients, moderate -23 patients, light - 30 patients. When compared with the prevalence of alleles in our region, a higher prevalence of S and Z anele was observed. When the patients were classified according to severity, the importance of the Z allele was verified in the more severe manifestation ofthe disease. The results obtained in this study suggest that the S and Z aneles are an additional risk factor for the development of asthma and that hese alleles may regulate disease severityMestradoCiencias BiomedicasMestre em Ciências Médica

Association Of Mbl2, Tgf-beta1 And Cd14 Gene Polymorphisms With Lung Disease Severity In Cystic Fibrosis.

To identify associations between genetic polymorphisms (in the MBL2, TGF-beta1 and CD14 genes) and the severity of the lung disease in patients with cystic fibrosis (CF), as well as between the presence of DeltaF508 alleles and lung disease severity in such patients. This was a cross-sectional cohort study, based on clinical and laboratory data, involving 105 patients with CF treated at a university hospital in the 2005-2006 period. We included 202 healthy blood donors as controls for the determination of TGF-beta1 and CD14 gene polymorphisms. Polymorphisms in the MBL2 and TGF-beta1 genes at codon 10, position +869, were genotyped using the allele-specific PCR technique. The C-159T polymorphism in the CD14 gene was genotyped using PCR and enzymatic digestion. Of the 105 CF patients evaluated, 67 presented with severe lung disease according to the Shwachman score. The MBL2 gene polymorphisms were not associated with disease severity in the CF patients. Analysis of the T869C polymorphism in the TGF-beta1 gene showed an association only between TC heterozygotes and mild pulmonary disease. Although patients presenting the TT genotype of the C159T polymorphism in the CD14 gene predominated, there was no significant difference regarding lung disease severity. There was an association between the TC genotype of the T869C polymorphism (TGF-beta1) and mild pulmonary disease in CF patients. In the CD14 gene, the TT genotype seems to be a risk factor for pulmonary disease but is not a modulator of severity. We found no association between being a DeltaF508 homozygote and presenting severe lung disease.35334-4

Associação entre deficiência de alfa-1-antitripsina e a gravidade da fibrose cística Association between alpha 1 antitrypsin deficiency and cystic fibrosis severity

OBJETIVO: Verificar a distribuição dos genótipos da alfa-1-antitripsina e correlacionar com a gravidade da doença pulmonar em pacientes fibrocísticos. MÉTODO: Estudo clínico-laboratorial de corte transversal, com 70 pacientes fibrocísticos do Hospital Universitário da UNICAMP. Os fibrocísticos tiveram diagnóstico confirmado clínica e laboratorialmente. A gravidade da fibrose cística foi avaliada pelo escore de Shwachman. Todos os pacientes foram analisados para os alelos S e Z de alfa-1-antitripsina usando a reação em cadeia da polimerase. RESULTADOS: Nove pacientes (12,8%) foram heterozigotos para os alelos S ou Z ou heterozigoto composto (SZ). Nenhuma diferença significativa foi encontrada na gravidade clínica da fibrose cística entre os genótipos da alfa-1-antitripsina. Nenhuma diferença com significância estatística foi encontrada quando os pacientes foram separados pela presença ou ausência da mutação deltaF508. CONCLUSÃO: Neste estudo, o primeiro realizado no Brasil sobre a associação entre deficiência de alfa-1-antitripsina e fibrose cística, não encontramos uma associação entre essa deficiência e a gravidade da fibrose cística.OBJECTIVE: To ascertain the distribution of alpha 1 antitrypsin genotypes and correlate it with the severity of pulmonary disease in patients with cystic fibrosis METHOD: A clinical and laboratory cross sectional study of 70 patients at the Universidade Estadual de Campinas teaching hospital. Cystic fibrosis diagnoses was confirmed by both clinical and laboratory methods. The severity of cystic fibrosis was evaluated by Shwachman score. All the patients were tested for the presence of S and Z alleles for alpha 1 antitrypsin deficiency using polymerase chain reaction. RESULTS: Nine (12.8%) patients were heterozygous for S or Z alleles or the heterozygote compound (SZ). No significant differences were found in clinical severity of Cystic fibrosis between genotypes of alpha 1 antitrypsin. No significant differences were found when the patients were divided according to the presence or absence of the deltaF508 mutation. CONCLUSION: In this study, the first undertaken in Brazil into the association of alpha 1 antitrypsin deficiency and cystic fibrosis, we did not find an association between the deficiency and cystic fibrosis severity