We hereby propose a novel approach to the identification of ischemic stroke (IS) susceptibility genes that involves converging data from several unbiased genetic and genomic tools. We tested the association between IS and genes differentially expressed between cases and controls, then determined which data mapped to previously reported linkage peaks and were nominally associated with stroke in published genome-wide association studies. We first performed gene expression profiling in peripheral blood mononuclear cells of 20 IS cases and 20 controls. Sixteen differentially expressed genes mapped to reported whole-genome linkage peaks, including the TTC7B gene, which has been associated with major cardiovascular disease. At the TTC7B locus, 46 tagging polymorphisms were tested for association in 565 Portuguese IS cases and 520 controls. Markers nominally associated in at least one test and defining associated haplotypes were then examined in 570 IS Spanish cases and 390 controls. Several polymorphisms and haplotypes in the intron 5-intron 6 region of TTC7B were also associated with IS risk in the Spanish and combined data sets. Multiple independent lines of evidence therefore support the role of TTC7B in stroke susceptibility, but further work is warranted to identify the exact risk variant and its pathogenic potential.

BackgroundThe genetic contribution to stroke is well established but it has proven difficult to identify the genes and the disease-associated alleles mediating this effect, possibly because only nuclear genes have been intensely investigated so far. Mitochondrial DNA (mtDNA) has been implicated in several disorders having stroke as one of its clinical manifestations. The aim of this case-control study was to assess the contribution of mtDNA polymorphisms and haplogroups to ischemic stroke risk.MethodsWe genotyped 19 mtDNA single nucleotide polymorphisms (SNPs) defining the major European haplogroups in 534 ischemic stroke patients and 499 controls collected in Portugal, and tested their allelic and haplogroup association with ischemic stroke risk.ResultsHaplogroup H1 was found to be significantly less frequent in stroke patients than in controls (OR = 0.61, 95% CI = 0.45–0.83, p = 0.001), when comparing each clade against all other haplogroups pooled together. Conversely, the pre-HV/HV and U mtDNA lineages emerge as potential genetic factors conferring risk for stroke (OR = 3.14, 95% CI = 1.41–7.01, p = 0.003, and OR = 2.87, 95% CI = 1.13–7.28, p = 0.021, respectively). SNPs m.3010G>A, m.7028C>T and m.11719G>A strongly influence ischemic stroke risk, their allelic state in haplogroup H1 corroborating its protective effect.ConclusionOur data suggests that mitochondrial haplogroup H1 has an impact on ischemic stroke risk in a Portuguese sample.

Cerebrovascular and cardiovascular diseases are the leading causes of death and disability worldwide. They are complex disorders resulting from the interplay of genetic and environmental factors, and may share several susceptibility genes. Several recent studies have implicated variants of the Kalirin (KALRN) gene with susceptibility to cardiovascular and metabolic phenotypes, but no studies have yet been performed in stroke patients. KALRN is involved, among others, in the inhibition of inducible nitric oxide synthase, in the regulation of ischemic signal transduction, and in neuronal morphogenesis, plasticity, and stability. The goal of the present study was to determine whether SNPs in the KALRN region on 3q13, which includes the Ropporin gene (ROPN1), predispose to ischemic stroke (IS) in a cohort of Portuguese patients and controls. We genotyped 34 tagging SNPs in the KALRN and ROPN1 chromosomal region on 565 IS patients and 517 unrelated controls, and performed genotype imputation for 405 markers on chromosome 3. We tested the singlemarker association of these SNPs with IS. One SNP (rs4499545) in the ROPN1-KALRN intergenic region and two SNPs in KALRN (rs17286604 and rs11712619) showed signiWcant (P < 0.05) allelic and genotypic (unadjusted and adjusted for hypertension, diabetes, and ever smoking) association with IS risk. Thirty-two imputed SNPs also showed an association at P < 0.05, and actual genotyping of Electronic supplementary material The online version of this article

In women with prior cerebral venous thrombosis, recurrent venous thrombotic events during subsequent pregnancies are infrequent.

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Submetido em 24/08/2014 Aceito para publicação em 23/03/2015 Resumo O quati (Nasua nasua) é uma espécie de ampla distribuição na América do Sul, inclusive no Brasil. O objetivo deste estudo foi observar e descrever a morfologia da ramiicação dos principais ramos arteriais das aortas torácica e abdominal do quati, comparando os achados com a literatura existente sobre as demais espécies domésticas e silvestres. Para este estudo foram utilizados dois exemplares machos adultos da espécie, coletados em rodovias do estado de Minas Gerais, mortos por atropelamento. Os espécimes foram ixados em solução formalina e tiveram os ramos aórticos preenchidos com látex para posterior dissecação e estudo. Observouse que a artéria subclávia esquerda é ramo direto do arco aórtico, não há formação de um tronco bicarotídeo nem de um tronco celíacomesentérico, fatos descritos de forma semelhante nos carnívoros domésticos. Dessa forma, notou-se que as ramiicações dos ramos arteriais da aorta do quati, tanto na cavidade torácica quanto abdominal, seguem uma distribuição muito semelhante à observada nos carnívoros domésticos, o que relete sua proximidade evolutiva dentro da ordem Carnivora. Com isso, esse estudo mostrou-se importante por aprofundar o conhecimento anatômico dessa espécie silvestre, permitindo que aspectos já conhecidos da medicina de cães sejam aplicados ao quati.

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O veado catingueiro (Mazama gouazoubira) é um ruminante silvestre de pelagem curta, marrom-acizentada, que vive nas Américas Central e do Sul. Objetivou-se descrever a formação da veia jugular externa em um exemplar macho que foi a óbito por atropelamento. As regiões da face e cervical foram dissecadas de modo a possibilitar a visualização da veia jugular externa e suas tributárias. Esta se formou a partir da união das veias maxilar e linguofacial. A primeira originou-se das veias temporal superficial e transversa da face, que em seu percurso recebeu as veias angular do olho, dorsal e lateral do nariz e labial superior. A segunda formou-se após a anastomose das veias lingual e facial. A veia facial originou-se da união das veias labial inferior e profunda da face, no terço médio da face, rostralmente ao músculo masseter. Esse arranjo vascular difere daquele comumente observado em ruminantes domésticos, nos quais a veia transversa da face se mostra pouco desenvolvida e a facial recebe as veias angular do olho, dorsais e lateral do nariz, além da labial superior. A veia jugular externa do veado catingueiro apresentou as mesmas tributárias que os ruminantes domésticos, porém, com arranjo vascular das veias facial e transversa da face de forma diferente.