Possible Associations of NTRK2 Polymorphisms with Antidepressant Treatment Outcome: Findings from an Extended Tag SNP Approach

Background: Data from clinical studies and results from animal models suggest an involvement of the neurotrophin system in the pathology of depression and antidepressant treatment response. Genetic variations within the genes coding for the brain-derived neurotrophic factor (BDNF) and its key receptor Trkb (NTRK2) may therefore influence the response to antidepressant treatment. Methods: We performed a single and multi-marker association study with antidepressant treatment outcome in 398 depressed Caucasian inpatients participating in the Munich Antidepressant Response Signature (MARS) project. Two Caucasian replication samples (N = 249 and N = 247) were investigated, resulting in a total number of 894 patients. 18 tagging SNPs in the BDNF gene region and 64 tagging SNPs in the NTRK2 gene region were genotyped in the discovery sample; 16 nominally associated SNPs were tested in two replication samples. Results: In the discovery analysis, 7 BDNF SNPs and 9 NTRK2 SNPs were nominally associated with treatment response. Three NTRK2 SNPs (rs10868223, rs1659412 and rs11140778) also showed associations in at least one replication sample and in the combined sample with the same direction of effects ($P_{corr}$ = .018, $P_{corr}$ = .015 and $P_{corr}$ = .004, respectively). We observed an across-gene BDNF-NTRK2 SNP interaction for rs4923468 and rs1387926. No robust interaction of associated SNPs was found in an analysis of BDNF serum protein levels as a predictor for treatment outcome in a subset of 93 patients. Conclusions/Limitations: Although not all associations in the discovery analysis could be unambiguously replicated, the findings of the present study identified single nucleotide variations in the BDNF and NTRK2 genes that might be involved in antidepressant treatment outcome and that have not been previously reported in this context. These new variants need further validation in future association studies

The genetic legacy of extreme exploitation in a polar vertebrate

Understanding the effects of human exploitation on the genetic composition of wild populations is important for predicting species persistence and adaptive potential. We therefore investigated the genetic legacy of large-scale commercial harvesting by reconstructing, on a global scale, the recent demographic history of the Antarctic fur seal (Arctocephalus gazella), a species that was hunted to the brink of extinction by 18th and 19th century sealers. Molecular genetic data from over 2,000 individuals sampled from all eight major breeding locations across the species’ circumpolar geographic distribution, show that at least four relict populations around Antarctica survived commercial hunting. Coalescent simulations suggest that all of these populations experienced severe bottlenecks down to effective population sizes of around 150–200. Nevertheless, comparably high levels of neutral genetic variability were retained as these declines are unlikely to have been strong enough to deplete allelic richness by more than around 15%. These findings suggest that even dramatic short-term declines need not necessarily result in major losses of diversity, and explain the apparent contradiction between the high genetic diversity of this species and its extreme exploitation history

Epidemiologia do carcinoma basocelular

O carcinoma basocelular é a neoplasia maligna mais comum em humanos e sua incidência vem aumentando nas últimas décadas. Sua grande frequência gera significativo ônus ao sistema de saúde, configurando problema de saúde pública. Apesar das baixas taxas de mortalidade e de rara ocorrência de metástases, o tumor pode apresentar comportamento invasivo local e recidivas após o tratamento, provocando importante morbidade. Exposição à radiação ultravioleta representa o principal fator de risco ambiental associado a sua gênese. Entretanto, descrevem-se outros elementos de risco: fotótipos claros, idade avançada, história familiar de carcinomas de pele, olhos e cabelos claros, sardas na infância e imunossupressão, além de aspectos comportamentais, como exercício profissional exposto ao sol, atividade rural e queimaduras solares na juventude. Entre 30% e 75% dos casos esporádicos estão associados à mutação do gene patched hedgehog, mas outras alterações genéticas são ainda descritas. A neoplasia é comumente encontrada concomitantemente com lesões cutâneas relacionadas à exposição solar crônica, tais como: queratoses actínicas, lentigos solares e telangiectasias faciais. A prevenção do carcinoma basocelular se baseia no conhecimento de fatores de risco, no diagnóstico e tratamento precoces e na adoção de medidas específicas, principalmente, nas populações susceptíveis. Os autores apresentam uma revisão da epidemiologia do carcinoma basocelular.Basal cell carcinoma is the most common malignant neoplasm in humans and its incidence has increased over the last decades. Its high frequency significantly burdens the health system, making the disease a public health issue. Despite the low mortality rates and the rare occurrence of metastases, the tumor may be locally invasive and relapse after treatment, causing significant morbidity. Exposure to ultraviolet radiation is the main environmental risk factor associated with its cause. However, other elements of risk are described, such as light skin phototypes, advanced age, family history of skin carcinoma, light eyes and blond hair, freckles in childhood and immunosuppression. Behavioral aspects such as occupational sun exposure, rural labor and sunburns at a young age also play a role. Between 30% and 75% of the sporadic cases are associated with patched hedgehog gene mutation, but other genetic changes are also described. The tumor is commonly found in concomitance with skin lesions related to chronic sun exposure, such as actinic keratoses, solar lentigines and facial telangiectasia. The prevention of basal cell carcinoma is based on the knowledge of risk factors, early diagnosis and treatment, as well as on the adoption of specific measures, particularly in susceptible populations. The authors present a review of the epidemiology of basal cell carcinoma

Fibrillin 1 gene with R2726W mutation is absent in patients with primary protrusio acetabuli and developmental dysplasia of the hip.

BACKGROUND: The morphological abnormality of the acetabulum in patients with primary protrusio acetabuli is almost the exact opposite as in those with developmental dysplasia of the hip. In primary protrusio acetabuli, the acetabulum is excessively deep, while in developmental dysplasia of the hip, the acetabulum is excessively shallow. A genetic etiology has been proposed in developmental dysplasia of the hip, while the etiology of primary protrusio acetabuli is widely debated. Primary protrusio acetabuli may represent a hitherto unidentified metabolic defect, and a possible candidate for such genetic influence is the R2726W variant of the fibrillin 1 (FBN1) gene, which segregates with isolated skeletal features of individuals with Marfan syndrome. MATERIAL/METHODS: We identified 26 patients with primary protrusio acetabuli and 45 patients with developmental dysplasia of the hip through clinical and radiographic examinations. We included 95 normal controls in the study. DNA from peripheral blood was used in genotyping for the FBN1 R2726W mutation using pyrosequencing. RESULTS: No mutant alleles were identified in any patients or controls. CONCLUSIONS: The R2726W mutation is not responsible for skeletal malformation of primary protrusio acetabuli in our population, although there may be unidentified genetic variants in either FBN1 or other genes that control acetabular morphology