TPH2 Gene Polymorphisms and Major Depression – A Meta-Analysis

BACKGROUND: Tryptophan hydroxylase-2 (TPH2) is the rate-limiting enzyme in the synthetic pathway for brain serotonin and is considered key factor for maintaining normal serotonin transmission in the central neuron system (CNS). Gene-disease association studies have reported a relationship between TPH2 and major depressive disorder (MDD) in different populations, however subsequent studies have produced contradictory results. OBJECTIVES: We performed a systematic overview and a meta-analysis with all available data up-to-date. METHODS: We scrutinized PubMed, Embase, HuGNet and China National Knowledge Infrastructure (CNKI ) and last update was held on October 2011. We also searched the manuscripts and the supplementary documents of the published genome-wide association studies in the field. Effect sizes of independent loci that have been studied in more than 3 articles were synthesized using fixed and random effects models. RESULTS: We found 27 eligible articles that studied a total of 74 single nucleotide polymorphisms (SNPs). Finally, 12 independent loci were included in the meta-analysis. The synthesis of the data shown that two SNPs (rs4570625 and rs17110747) were associated with MDD using fixed effects models. SNP rs4570625 had low heterogeneity and remained significant using the more conservative random effects calculations with a summary OR = 0.83 (95% CI: 0.73-0.96). CONCLUSION: The current study identified a SNP (rs4570625) with strong epidemiological credibility; however more studies are required to provide robust evidence for other weak associations

Comparação entre dois métodos de avaliação do controle da asma baseados na percepção individual Comparison between two methods of asthma control evaluation based on individual perception

OBJETIVO: Comparar a percepção subjetiva do controle da asma informada pelo paciente com aquela obtida por meio do escore do Asthma Control Questionnaire com seis questões (ACQ-6) em pacientes com asma grave e verificar se o controle da asma está associado ao número de visitas a salas de emergência no mês anterior. MÉTODOS: Estudo transversal de 528 pacientes acompanhados na Central de Referência do Programa para Controle da Asma e Rinite Alérgica na Bahia, entre agosto de 2008 e março de 2010, em Salvador (BA). Os pacientes responderam ao ACQ-6 e a uma questão adicional específica para avaliar sua percepção do controle da doença na semana prévia. RESULTADOS: Foram avaliados 423 pacientes, que preencheram os critérios de inclusão. A maioria era do gênero feminino (81,3%) e possuía renda familiar menor que dois salários mínimos (64,3%). A média de idade foi de 49,85 ± 13,71 anos, e a duração dos sintomas de asma foi de 32,11 ± 16,35 anos. Os pacientes eram regularmente tratados no programa há 36,65 ± 18,10 meses. Baseados na percepção subjetiva do controle, 8% dos pacientes consideraram a sua asma não controlada, enquanto 38,8% obtiveram escore do ACQ > 1,5, indicando falta de controle. O coeficiente kappa revelou fraca concordância entre os dois métodos. Houve uma associação direta entre falta de controle e número de visitas a emergência no mês anterior (p < 0,001). CONCLUSÕES: Nesta amostra de pacientes, a percepção subjetiva do paciente sobre o controle da asma diferiu da medida por meio do ACQ-6, e os pacientes superestimaram seu controle, trazendo risco de subtratamento.<br>OBJECTIVE: To compare the subjective perception of asthma control reported by the patient with that measured by the score obtained on the Asthma Control Questionnaire 6-item version (ACQ-6) in patients with severe asthma and to determine whether asthma control is associated with the number of emergency room visits in the previous month. METHODS: This was a cross-sectional study involving 528 patients treated at the Bahia State Asthma and Allergic Rhinitis Control Program Central Referral Clinic between August of 2008 and March of 2010, in the city of Salvador, Brazil. The patients completed the ACQ-6 and answered a specific additional question in order to evaluate their own perception of asthma control in the previous week. RESULTS: We evaluated 423 patients who met the inclusion criteria. The sample was predominantly female (81.3%), and 64.3% had an income lower than two times the national minimum wage. The mean age was 49.85 ± 13.71 years, and the duration of asthma symptoms was 32.11 ± 16.35 years. The patients had been regularly treated via the program for 36.65 ± 18.10 months. Based on the subjective perception of asthma control, only 8% of the patients considered their asthma to be uncontrolled, whereas 38.8% had an ACQ-6 score > 1.5, which indicates poor control. The kappa statistic revealed poor concordance between the two methods. There was a direct association between uncontrolled asthma and the number of emergency room visits in the previous month (p < 0.001). CONCLUSIONS: In this sample of patients, the subjective perception of asthma control differed from that measured by the ACQ-6 score, and the patients overestimated their own level of asthma control, which puts them at risk of being undertreated