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

Detection of human bocavirus and human metapneumovirus by real-time PCR from patients with respiratory symptoms in Southern Brazil

The introduction of newer molecular methods has led to the discovery of new respiratory viruses, such as human metapneumovirus (hMPV) and human bocavirus (hBoV), in respiratory tract specimens. We have studied the occurrence of hMPV and hBoV in the Porto Alegre (PA) metropolitan area, one of the southernmost cities of Brazil, evaluating children with suspected lower respiratory tract infection from May 2007-June 2008. A real-time polymerase chain reaction method was used for amplification and detection of hMPV and hBoV and to evaluate coinfections with respiratory syncytial virus (RSV), influenza A and B, parainfluenza 1, 2 and 3, human rhinovirus and human adenovirus. Of the 455 nasopharyngeal aspirates tested, hMPV was detected in 14.5% of samples and hBoV in 13.2%. A unique causative viral agent was identified in 46.2% samples and the coinfection rate was 43.7%. For hBoV, 98.3% of all positive samples were from patients with mixed infections. Similarly, 84.8% of all hMPV-positive results were also observed in mixed infections. Both hBoV and hMPV usually appeared with RSV. In summary, this is the first confirmation that hMPV and hBoV circulate in PA; this provides evidence of frequent involvement of both viruses in children with clinical signs of acute viral respiratory tract infection, although they mainly appeared as coinfection agents

Mucopolysaccharidoses in northern Brazil: Targeted mutation screening and urinary glycosaminoglycan excretion in patients undergoing enzyme replacement therapy

Mucopolysaccharidoses (MPS) are rare lysosomal disorders caused by the deficiency of specific lysosomal enzymes responsible for glycosaminoglycan (GAG) degradation. Enzyme Replacement Therapy (ERT) has been shown to reduce accumulation and urinary excretion of GAG, and to improve some of the patients’ clinical signs. We studied biochemical and molecular characteristics of nine MPS patients (two MPS I, four MPS II and three MPS VI) undergoing ERT in northern Brazil. The responsiveness of ERT was evaluated through urinary GAG excretion measurements. Patients were screened for eight common MPS mutations, using PCR, restriction enzyme tests and direct sequencing. Two MPS I patients had the previously reported mutation p.P533R. In the MPS II patients, mutation analysis identified the mutation p.R468W, and in the MPS VI patients, polymorphisms p.V358M and p.V376M were also found. After 48 weeks of ERT, biochemical analysis showed a significantly decreased total urinary GAG excretion in patients with MPS I (p < 0.01) and MPS VI (p < 0.01). Our findings demonstrate the effect of ERT on urinary GAG excretion and suggest the adoption of a screening strategy for genotyping MPS patients living far from the main reference centers

Identification Of β Thalassemia Mutations In South Brazilians

We have evaluated the mutation profile in a sample of 127 unrelated β-thalassemia (β thal) individuals, diagnosed through A2 and fetal hemoglobin quantification by high-performance liquid chromatography (HPLC) from the Brazilian southernmost state, where a flow of Italian immigrants had occurred in the late 19th century, mainly from Northern Italy. The molecular analysis was performed by DNA sequencing of the most common mutations found in the Mediterranean region. The β0 codon 39 nonsense mutation was the most frequent alteration (50.9%), followed by β+ IVSI 110 G&gt;A (18.1%), β0 IVSI 1 G&gt;A (12.9%), β+ IVSI 6 T&gt;C (9.5%), and other rare mutations (8.6%). The chosen gene sequence was able to identify 91% β-thal mutations in the population studied, showing some similarity with allele frequencies of the mainly colonizing countries of Rio Grande do Sul state. The comparison of our results to other Brazilian studies has shown significant differences. Therefore, we can conclude that the genotypic profile of β-thal shows great variability. Hence, it would be arbitrary to infer regional study results as being representative of the Brazilian whole population. Brazilian researchers of different regions should identify their most frequent genotypes to provide better understanding on this disease and state adequate public health policies. © Springer-Verlag 2007.875381384Araujo, A.S., Silva, W.A., Leao, S.A., Bandeira, F.C., Petrou, M., Modell, B., Zago, M.A., A different molecular patterns of beta-thalassemia mutation in northeast Brazil (2003) Hemoglobin, 27, pp. 211-217Bertuzzo, C.S., Sonati, M.F., Costa, F.F., Hematological phenotype and the type of β-thalassemia mutation in Brazil (1997) Braz. J. Genet., 20, pp. 319-321Beutler, E., Discrepancies between genotype and phenotype in hematology: An important frontier (2001) Blood, 98, pp. 2597-2602Cao, A., Rosatelli, C., Pirastu, M., Galanello, R., Thalassemias in Sardinia: Molecular pathology, phenotype-genotype correlation, and prevention (1991) Am J Pediatr Hematol Oncol, 13, pp. 179-188Chouk, I., Daoud, B.B., Mellouli, F., Bejaouli, F., Gerard, N., Dellagi, K., Abbes, S., Contribution to the description of the beta-thalassemia spectrum in Tunisia and the origin of mutation diversity (2004) Hemoglobin, 28, pp. 189-195Faustino, P., Pacheco, P., Loureiro, P., Nogueira, P.J., Lavinha, J., The geographic pattern of beta-thalassaemia mutations in the portuguese population (1999) Br J Haematol, 107, pp. 903-904Freitas, E.M., Rocha, F.J., Detection of beta-thalassemia heterozygotes among caucasians from Porto Alegre, RS, Brazil (1983) Rev Bras Gen, 6, pp. 185-188Frosi, V.M., Mioranza, C., Inícios da Imigração - Processos de estabelecimento (1975) Imigração Italiana No Nordeste Do Rio Grande Do Sul, pp. 38-42. , In: Frosi VM, Mioranza C (eds) Co-edições Universidade de Caxias do Sul/Instituto Superior Brasileiro Italiano de Estudos e Pesquisas. Porto Alegre, MovimentoHuisman, T.H.J., Carver, M.F.H., Bysal, E., (1997) A Syllabus of Thalassemia Mutations, , The Sickle Cell Anemia Foundation, Augusta, USAKattamis, C., Hu, H., Cheg, G., Reese, A.L., Gonzalez, R.J.M., Kutlar, A., Kutlar, F., Huisman, T.H., Molecular characterization of beta-thalassaemia in 174 Greek patients with thalassaemia major (1990) Br J Haematol, 74, pp. 342-346Kimura, E.M., Grignoli, C.R., Pinheiro, V.R., Costa, F.F., Sonati, M.F., Thalassemia intermedia as a result of heterozygosis for beta 0-thalassemia and alpha alpha alpha anti-3,7 genotype in a Brazilian patient (2003) Braz J Med Biol Res, 36, pp. 699-701Magro, S., Santilli, E., Mancuso, R., Puzzonia, P., Consarino, C., Morgione, S., Galati, M.C., Molica, S., Spectrum of β-thalassemia mutations in Calabria: Implications for prenatal diagnosis (1995) Am J Hematol, 48, pp. 128-129Miranda, S.R.P., Fonseca, S.F., Figueiredo, M.S., Yamamoto, M., Grotto, H.Z.W., Saad, S.T.O., Hb Köln [a2b298(FG5) val-met] identified by DNA analysis in a Brazilian family (1997) Braz J Genet, 20 (4), pp. 745-748Parra, F.C., Amado, R.C., Lambertucci, J.R., Rocha, J., Antunes, C.M., Pena, S.D., Color and genomic ancestry in Brazilians (2003) Proc Natl Acad Sci USA, 100, pp. 177-182Rady, M.S., Baffico, M., Khalifa, A.S., Heshmat, N.M., El-Moselhy, S., Sciarratta, G.V., Identification of Mediterranean beta-thalassemia mutations by reverse dot-blot in Italians and Egyptians (1997) Hemoglobin, 21, pp. 59-69Ribeiro, M.L., Gonçalves, P., Cunha, E., Genetic heterogeneity of β-thalassemia in populations of the Iberian peninsula (1997) Hemoglobin, 21, pp. 261-269Riou, J., Godart, C., Hurtrel, D., Mathis, M., Bimet, C., Bardakdjian-Michau, J., Prehu, C., Galacteros, F., Cation-exchange HPLC evaluated for presumptive identification of hemoglobin variants (1997) Clin Chem, 43, pp. 34-39Rosatelli, M.C., Tuveri, T., Scalas, M.T., Leoni, G.B., Sardu, R., Faa, V., Meloni, A., Monni, G., Molecular screening and fetal diagnosis of beta-thalassemia in the italian population (1992) Hum Genet, 89, pp. 585-589Rund, D., Rachmilewitz, E., -Thalassemia (2005) N Engl J Med, 353, pp. 1135-1146Salzano, F.M., Bortolini, M.C., (2002) The Evolution and Genetics of Latin American Populations, , Cambridge University Press, CambridgeSchilirò, G., Di Gregorio, F., Samperi, P., Mirabile, E., Liang, R., Cürük, M.A., Ye, Z., Huismann, T.H.J., Genetic heterogeneity of β-thalassemia in Southeast Sicily (1995) Am J Hematol, 48, pp. 5-11Silva, D.R., Santos, F.R., Rocha, J., Pena, S.D., The phylogeography of Brazilian Y-chromosome lineages (2001) Am J Hum Genet, 68, pp. 281-286Weimer, T.A., Salzano, F.M., Hutz, M.H., Erythrocyte isozymes and hemoglobin types in a southern Brazilian population (1981) J Hum Evol, 10, pp. 319-328Zembrzuski, V.M., Callegari-Jacques, S.M., Hutz, M.H., Application of an African ancestry index as a genomic control approach in a Brazilian population (2006) Ann Hum Genet, 70 (PART 6), pp. 822-82

Diagnostic and treatment strategies in mucopolysaccharidosis VI

Filippo Vairo,1&ndash;3 Andressa Federhen,1,3,4 Guilherme Baldo,1,2,5&ndash;7 Mariluce Riegel,1,6 Maira Burin,1 Sandra Leistner-Segal,1,8 Roberto Giugliani1,5,6,81Medical Genetics Service, Hospital de Cl&iacute;nicas de Porto Alegre, Porto Alegre, Brazil; 2Department of Genetics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; 3Clinical Research Group on Medical Genetics, Hospital de Cl&iacute;nicas de Porto Alegre, Porto Alegre, Brazil; 4Post-Graduate Program in Child and Adolescent Health, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; 5Gene Therapy Center, Hospital de Cl&iacute;nicas de Porto Alegre, Porto Alegre, Brazil; 6Post-Graduate Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; 7Department of Physiology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; 8Post-Graduate Program in Medical Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, BrazilAbstract: Mucopolysaccharidosis VI (MPS VI) is a very rare autosomal recessive disorder caused by mutations in the ARSB gene, which lead to deficient activity of the lysosomal enzyme ASB. This enzyme is important for the breakdown of the glycosaminoglycans (GAGs) dermatan sulfate and chondroitin sulfate, which accumulate in body tissues and organs of MPS VI patients. The storage of GAGs (especially dermatan sulfate) causes bone dysplasia, joint restriction, organomegaly, heart disease, and corneal clouding, among several other problems, and reduced life span. Despite the fact that most cases are severe, there is a spectrum of severity and some cases are so attenuated that diagnosis is made late in life. Although the analysis of urinary GAGs and/or the measurement of enzyme activity in dried blood spots are useful screening methods, the diagnosis is based in the demonstration of the enzyme deficiency in leucocytes or fibroblasts, and/or in the identification of pathogenic mutations in the ARSB gene. Specific treatment with enzyme replacement has been available since 2005. It is safe and effective, bringing measurable benefits and increased survival to patients. As several evidences indicate that early initiation of therapy may lead to a better outcome, newborn screening is being considered for this condition, and it is already in place in selected areas where the incidence of MPS VI is increased. However, as enzyme replacement therapy is not curative, associated therapies should be considered, and research on innovative therapies continues. The management of affected patients by a multidisciplinary team with experience in MPS diseases is highly recommended.Keywords: mucopolysaccharidosis VI, Maroteaux&ndash;Lamy syndrome, dermatan sulfate, arylsulfatase b, enzyme replacement therapy, lysosomal storage disease