Analysis of R213R and 13494 g→a polymorphisms of the p53 gene in individuals with esophagitis, intestinal metaplasia of the cardia and Barrett’s Esophagus compared with a control group

Protein p53 is the tumor suppressor involved in cell cycle control and apoptosis. There are several polymorphisms reported for p53 which can affect important regions involved in protein tumor suppressor activity. Amongst the polymorphisms described, R213R and 13949 g→a are rarely studied, with an estimate frequency not yet available for the Brazilian population. The purpose of this study was to investigate the genotype and allele frequencies and associations of these polymorphisms in a group of patients with altered esophageal tissue from South Brazil and compare with the frequency observed for a control population. A total of 35 patients for R213R and 45 for 13494 g→a polymorphisms analysis with gastroesophageal reflux disease (GERD) symptoms diagnosed by upper digestive endoscopy and confirmed by biopsy were studied. For both groups, 100 controls were used for comparison. Loss of heterozygosity (LOH) was also analyzed for a selected group of patients where normal and affected tissue was available. There was one patient with Barrett’s Esophagus (BE) showing LOH for R213R out of two heterozygous samples analyzed and two patients (esophagitis and BE) for 13494 g→a polymorphism. We also aimed to build a haplotype for both polymorphisms collectively analyzed with R27P polymorphism, previously reported by our group. There were no significant differences in allele and genotype distribution between patients and controls. Although using esophagitis, intestinal metaplasia of the cardia and BE samples, all non-neoplastic lesions, we can conclude that these sites do not represent genetic susceptibility markers for the development and early progression of GERD to BE and esophageal cancer. Additional studies are required in order to investigate other determiners of early premalignant lesions known to predispose to esophageal cancer

Lack of association between the Serotonin Transporter Promoter Polymorphism (5-HTTLPR) and Panic Disorder: a systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>The aim of this study is to assess the association between the Serotonin Transporter Promoter Polymorphism (5-HTTLPR) and Panic Disorder (PD).</p> <p>Methods</p> <p>This is a systematic review and meta-analysis of case-control studies with unrelated individuals of any ethnic origin examining the role of the 5-HTTLPR in PD according to standard diagnostic criteria (DSM or ICD). Articles published in any language between January 1996 and April 2007 were eligible. The electronic databases searched included PubMed, PsychInfo, Lilacs and ISI. Two separate analyses were performed: an analysis by alleles and a stratified analysis separating studies by the quality of control groups. Asymptotic DerSimonian and Laird's Q test were used to assess heterogeneity. Results of individual studies were combined using the fixed effect model with respective 95% confidence intervals.</p> <p>Results</p> <p>Nineteen potential articles were identified, and 10 studies were included in this meta-analysis. No statistically significant association between 5-HTTLPR and PD was found, OR = 0.91 (CI95% 0.80 to 1.03, p = 0.14). Three sub-analyses divided by ethnicity, control group quality and Agoraphobia comorbidity also failed to find any significant association. No evidence of heterogeneity was found between studies in the analyses.</p> <p>Conclusion</p> <p>Results from this systematic review do not provide evidence to support an association between 5-HTTLPR and PD. However, more studies are needed in different ethnic populations in order to evaluate a possible minor effect.</p

Prevalence of thrombophilia and thrombotic events in patients with fabry disease in a Reference Center for Lysosomal Disorders in Southern Brazil

Introduction: Venous thromboembolism (VTE) is a multifactorial genetic disorder that occurs in approximately one in a thousand adults per year. Because there is no laboratory test or clinical marker useful for predicting which patients with Fabry disease may develop thrombotic events, this study aimed to determine whether there is a hereditary predisposition to hypercoagulation in these patients. Methods: The prevalence of p.R506Q mutation in the factor V gene and of c.G20210A mutation in Factor II (prothrombin) gene was evaluated in 39 patients with Fabry disease fromSouthern Brazil and correlated with clinical findings. The DNA analysis was performed by real-time polymerase chain reaction on genomic DNA using TaqMan probes. Results: In this group of patients, the frequency of mutation in the prothrombin gene was 1.28%, whereas no patient showed mutation in the factor V gene; additionally, there was no correlation between these mutations and the incidence of thrombotic events. Conclusion: Hereditary thrombophilia due to mutations in factor V and prothrombin genes does not seem to be related to thrombotic events in Fabry patients in our cohort, although studies in larger cohorts and the inclusion of additional factors may be required to determine if a correlation exists.     Introdução: O tromboembolismo venoso (TEV) é uma desordem genética multifatorial que ocorre em aproximadamente um em cada mil adultos por ano. Pelo fato de não existir nenhum teste de laboratório ou marcador clínico útil para predizer quais pacientes com a doença de Fabry podem desenvolver eventos trombóticos, este estudo foi realizado com o objetivo de determinar se existe uma predisposição hereditária para hipercoagulação nesses pacientes. Métodos: A prevalência da mutação p.R506Q no gene do fator V e da mutação c.G20210A no gene do fator II (protrombina) foi avaliada em 39 pacientes com doença de Fabry do Sul do Brasil e associada com achados clínicos. A análise do DNA genômico foi realizada por reação em cadeia da polimerase (polymerase-chain reaction, PCR) em tempo real utilizando sondas TaqMan. Resultados: Neste grupo de pacientes, a frequência da mutação no gene da protrombina foi de 1,28%, enquanto que nenhum paciente apresentou a mutação no gene do fator V, não havendo correlação entre essas mutações e a incidência de eventos trombóticos. Conclusão: A trombofilia hereditária devido às mutações nos genes fator V e protrombina parece não estar relacionada a eventos trombóticos em pacientes com Fabry em nossa coorte, embora estudos em coortes maiores e a inclusão de fatores adicionais possam ser necessários para determinar se existe uma correlação