Browsing by Author "Viana-Baptista, M"
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- Kalirin: a novel genetic risk factor for ischemic strokePublication . Krug, T; Manso, H; Gouveia, L; Sobral, J; Xavier, J; Albergaria, I; Gaspar, G; Correia, M; Viana-Baptista, M; Simões, R; Pinto, A; Taipa, R; Ferreira, C; Fontes, J; Silva, M; Gabriel, J; Matos, I; Lopes, G; Ferro, J; Vicente, A; Oliveira, SCerebrovascular 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 single-marker association of these SNPs with IS. One SNP (rs4499545) in the ROPN1-KALRN intergenic region and two SNPs in KALRN (rs17286604 and rs11712619) showed significant (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 three of these polymorphisms (rs7620580, rs6438833, and rs11712039) validated their association. Furthermore, rs11712039 was associated with IS (0.001 < P < 0.01) in a recent well-powered genomewide association study (Ikram et al. 2009). These studies suggest that variants in the KALRN gene region constitute risk factors for stroke and that KALRN may represent a common risk factor for vascular diseases.
- Mitochondrial haplogroup H1 is protective for ischemic stroke in Portuguese patients.Publication . Rosa, A; Fonseca, B; Krug, T; Manso, H; Gouveia, L; Albergaria, I; Gaspar, G; Correia, M; Viana-Baptista, M; Simões, R; Pinto, A; Taipa, R; Ferreira, C; Fontes, J; Silva, M; Gabriel, J; Matos, I; Lopes, G; Ferro, J; Vicente, A; Oliveira, SBACKGROUND: The 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. METHODS: We 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. RESULTS: Haplogroup 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. CONCLUSION: Our data suggests that mitochondrial haplogroup H1 has an impact on ischemic stroke risk in a Portuguese sample.
- Stroke in adults with Down syndrome.Publication . Marto, J; Dias, M; Alves, J; Montes, V; Beato-Coelho, J; Marques-Matos, C; Sousa, A; Bernardo, F; Calado, S; Viana-Baptista, M
- Vascular White Matter Lesions in Young Adults: A Neurology Outpatient Clinic RegistryPublication . Viana-Baptista, M; Cruz-e-Silva, V; Caetano, A; Marto, JP; Azevedo, E; Ferreira, C; Pinto, AA, et al.Introduction: Although frequently assumed to be age-related changes, vascular white matter lesions (WML) are sometimes found in young adults. Etiology is usually attributed to sporadic small vessel disease; nevertheless, genetic disorders may also be implicated. We aimed to characterize the population of young adults with vascular WML in Neurology outpatient clinics. Methods: Neurologists from 12 Portuguese hospitals were invited to include patients aged 18-55 years evaluated in consultation, with vascular WML on MRI, scoring II or III in the Fazekas scale. Central imaging validation was performed by 2 independent, blinded, Neuroradiologists. Demographic and clinical data were collected as well as results of investigations performed. Results: During 2 years, 77 patients were included (mean age 47.7 years). Vascular risk factors were present in 88.3% patients (hypertension in 53.2%) and previous history of stroke in 36.4%. Patients without history of stroke were younger (46.6 ± 7.2 vs. 49.6 ± 3.9 years, p = 0.045) and had fewer vascular risk factors (p < 0.001). They were more frequently females (87.8 vs. 46.4%, p < 0.001), and headache (30.6 vs. 3.6%, p = 0.007), contrary to focal symptoms (16.3 vs. 53.6%, p = 0.001), was the most frequent reason of referral. Etiological investigations performed differed between Neurologists. A genetic disorder was identified in 6 out of 58 patients (CADASIL n = 5; COL4A1 n = 1). Conclusion: Young adults with vascular WML evaluated in Neurology outpatient clinics concentrate in the oldest age groups. Vascular risk factors should be screened carefully in this population. Among patients without history of stroke, females largely outweigh males. Diagnostic investigations performed do not follow a standardized protocol.