Genetic variation in the tau protein phosphatase-2A pathway is not associated with Alzheimer's disease risk

<p>Abstract</p> <p>Background</p> <p>Tau abnormal hyperphosphorylation and the formation of neurofibrillary tangles in AD brain is the result of upregulation of tau kinases and downregulation of tau phosphatases.</p> <p>Methods</p> <p>In a group of 729 Spanish late-onset Alzheimer's disease (AD) patients and 670 healthy controls, we examined variations into a set of candidate genes (PPP2CA, PPP2R2A, ANP32A, LCMT1, PPME1 and PIN1) in the tau protein phosphatase-2A (PP2A) pathway, to address hypotheses of genetic variation that might influence AD risk.</p> <p>Results</p> <p>There were no differences in the genotypic, allelic or haplotypic distributions between cases and controls in the overall analysis or after stratification by age, gender or APOE ε4 allele.</p> <p>Conclusion</p> <p>Our negative findings in the Spanish population argue against the hypothesis that genetic variation in the tau protein phosphatase-2A (PP2A) pathway is causally related to AD risk</p

Implications of the polymorphism of HLA-G on its function, regulation, evolution and disease association

The HLA-G gene displays several peculiarities that are distinct from those of classical HLA class I genes. The unique structure of the HLA-G molecule permits a restricted peptide presentation and allows the modulation of the cells of the immune system. Although polymorphic sites may potentially influence all biological functions of HLA-G, those present at the promoter and 3′ untranslated regions have been particularly studied in experimental and pathological conditions. The relatively low polymorphism observed in the MHC-G coding region both in humans and apes may represent a strong selective pressure for invariance, whereas, in regulatory regions several lines of evidence support the role of balancing selection. Since HLA-G has immunomodulatory properties, the understanding of gene regulation and the role of polymorphic sites on gene function may permit an individualized approach for the future use of HLA-G for therapeutic purposes

Prevalence of alcohol and tobacco use among Brazilian adolescents: a systematic review

OBJECTIVE: To analyze alcohol and tobacco use among Brazilian adolescents and identify higher-risk subgroups. METHODS: A systematic review of the literature was conducted. Searches were performed using four databases (LILACS, MEDLINE /PubMed, Web of Science, and Google Scholar), specialized websites and the references cited in retrieved articles. The search was done in English and Portuguese and there was no limit on the year of publication (up to June 2011). From the search, 59 studies met all the inclusion criteria: to involve Brazilian adolescents aged 10-19 years; to assess the prevalence of alcohol and/or tobacco use; to use questionnaires or structured interviews to measure the variables of interest; and to be a school or population-based study that used methodological procedures to ensure representativeness of the target population (i.e. random sampling). RESULTS: The prevalence of current alcohol use (at the time of the investigation or in the previous month) ranged from 23.0% to 67.7%. The mean prevalence was 34.9% (reflecting the central trend of the estimates found in the studies). The prevalence of current tobacco use ranged from 2.4% to 22.0%, and the mean prevalence was 9.3%. A large proportion of the studies estimated prevalences of frequent alcohol use (66.7%) and heavy alcohol use (36.8%) of more than 10%. However, most studies found prevalences of frequent and heavy tobacco use of less than 10%. The Brazilian literature has highlighted that environmental factors (religiosity, working conditions, and substance use among family and friends) and psychosocial factors (such as conflicts with parents and feelings of negativeness and loneliness) are associated with the tobacco and alcohol use among adolescents. CONCLUSIONS: The results suggest that consumption of alcohol and tobacco among adolescents has reached alarming prevalences in various localities in Brazil. Since unhealthy behavior tends to continue from adolescence into adulthood, public policies aimed towards reducing alcohol and tobacco use among Brazilians over the medium and long terms may direct young people and the subgroups at higher risk towards such behavior

Fatores associados à experimentação do cigarro em adolescentes Factors associated with cigarette experimentation among adolescents

OBJETIVO: Analisar a prevalência e os fatores associados à experimentação do cigarro em adolescentes. MÉTODOS: Estudo transversal, utilizando-se questionário específico, onde foram entrevistados 2.883 estudantes do ensino fundamental e do 1º ano do ensino médio, de escolas localizadas na zona urbana da cidade de Cuiabá (MT). Estimou-se a prevalência e foram analisados os principais fatores relacionados à experimentação do cigarro. Após isso, obteve-se um modelo logístico hierarquizado descrevendo as chances da experimentação do cigarro relacionada com as variáveis investigadas. RESULTADOS: A prevalência da experimentação do cigarro foi de 30,2%. No modelo final de análise, as principais variáveis relacionadas com a experimentação do cigarro foram menor nível de escolaridade da mãe (OR = 2,44; IC95%: 1,72-3,47); menor nível socioeconômico (OR = 1,39; IC95%: 1,01-1,93); estudar na escola pública (OR = 1,56; IC95%: 1,22-2,00); estar no 1º ano do ensino médio (OR = 3,45; IC95%: 2,63-4,54); estudar no período noturno (OR = 2,44; 1,85-3,22); ter pais separados (OR = 1,23; IC95%: 1,02-1,49); já ter sido reprovado na escola (OR = 2,17; IC95%: 1,78-2,70); ter amigos fumantes (OR = 3,75; IC95%: 2,99-4,70); ter irmãos fumantes (OR = 2,44; IC95%: 1,82-3,27); e ser mais velho (17-19 anos) (OR = 2,44; IC95%: 1,39-4,17). CONCLUSÕES: Foi alta proporção de adolescentes que experimentaram o cigarro. Após ajuste para variáveis de confusão os fatores mais fortemente associados à experimentação do cigarro foram nível de escolaridade da mãe, idade do adolescente, estudar no período noturno, já ter sido reprovado na escola e ter amigos e irmãos fumantes. Medidas preventivas devem ser direcionadas aos adolescentes, dentro das instituições escolares, como forma de controle do tabagismo.OBJECTIVE: To assess the prevalence of and factors associated with smoking experimentation among adolescents. METHODS: Cross-sectional study, using a specific questionnaire to interview 2,883 students from 7th to 10th grade in schools located in the urban area of the city of Cuiabá, in the state of Mato Grosso, Brazil. Prevalence was estimated, and the principal factors related to cigarette experimentation were analyzed. Subsequently, a hierarchical logistic model was used to describe the chances of cigarette experimentation related to the variables being investigated. RESULTS: The prevalence of cigarette experimentation was 30.2%. In the final model of the analysis, the main variables related to cigarette experimentation were low maternal level of education (OR = 2.44; 95% CI: 1.72-3.47); low socioeconomic level (OR=1.39; 95% CI: 1.01-1.93); studying in a public school (OR = 1.56; 95% CI: 1.22-2.00); being in 10th grade (OR = 3.45; 95% CI: 2.63-4.54); attending school in the evening (OR = 2.44; 95% CI: 1.85-3.22); having divorced parents (OR = 1.23; 95% CI: 1.02-1.49); having been held back for one school year (OR = 2.17; 95% CI: 1.78-2.70); having friends who smoke (OR = 3.75; 95% CI: 2.99-4.70) having a sibling who smokes (OR = 2.44; 95% CI: 1.82-3.27); and being older (age 17-19 years) (OR = 2.44; 95% CI: 1.39-4.17). CONCLUSIONS: A high proportion of adolescents have experimented with smoking. After adjusting for confounding variables, the factors most strongly associated with cigarette experimentation were maternal level of education, age of the adolescent, attending school in the evening, having been held back for one school year and having a sibling who smokes. Preventive measures must be directed at adolescents in schools in order to control smoking

PIN1 gene variants in Alzheimer's disease

Background: Peptidyl-prolyl isomerase, NIMA-interacting 1 (PIN1) plays a significant role in the brain and is implicated in numerous cellular processes related to Alzheimer's disease (AD) and other neurodegenerative conditions. There are confounding results concerning PIN1 activity in AD brains. Also PIN1 genetic variation was inconsistently associated with AD risk. Methods: We performed analysis of coding and promoter regions of PIN1 in early-and late-onset AD and frontotemporal dementia (FTD) patients in comparison with healthy controls. Results: Analysis of eighteen PIN1 common polymorphisms and their haplotypes in EOAD, LOAD and FTD individuals in comparison with the control group did not reveal their contribution to disease risk. In six unrelated familial AD patients four novel PIN1 sequence variants were detected. c.58+64C&gt;T substitution that was identified in three patients, was located in an alternative exon. In silico analysis suggested that this variant highly increases a potential affinity for a splicing factor and introduces two intronic splicing enhancers. In the peripheral leukocytes of one living patient carrying the variant, a 2.82 fold decrease in PIN1 expression was observed. Conclusion: Our data does not support the role of PIN1 common polymorphisms as AD risk factor. However, we suggest that the identified rare sequence variants could be directly connected with AD pathology, influencing PIN1 splicing and/or expression.</p