Browsing by Author "Paulos-Pinheiro, S."
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- A genome-wide association study using a DNA pooling strategy identifies BBS9 and GLIS3 as novel loci influencing patient’s outcome after strokePublication . Manso, H.; Paulos-Pinheiro, S.; Krug, T.; Sobral, J.; Albergaria, I.; Gaspar, G.; Ferro, J.M.; Oliveira, S.A.; Vicente, A.M.Stroke is a major cause of morbidity in developed countries and therefore finding adequate treatments to promote patient’s recovery is a priority task, requiring the elucidation of the molecular pathways influencing brain recovery. Few studies, however, have assessed the role of genes in stroke outcome. This study describes a pilot genome-wide association study (GWAS) to identify genetic factors contributing to patient’s outcome, using a DNA pooling design. Methods: Patient’s outcome was assessed using the modified Rankin Scale (mRS) three months after stroke. Using the 250K Affymetrix GeneChip Mapping Assay® – Nsp I, we compared SNP allele frequencies in a pool of non-disabled stroke patients (N=87, mRS=0), with a pool of severely disabled or deceased patients (N=100, mRS>=3). The 100 most interesting SNPs were selected for validation by individual genotyping. Results: 36 SNPs were validated, showing significant differences between patients with extremely good and extremely poor outcome at three months (1.7x10-4 ).
- The role of ADH1B in alcohol consumption and stroke susceptibilityPublication . Paulos-Pinheiro, S.; Coelho, J.I.; Albergaria, I.; Gaspar, G.; Ferro, J.M.; Vicente, A.M.While heavy episodic drinking has been shown to be harmful to the heart, moderate alcohol consumption is thought to be protective against cardiovascular disease, through the regulation of rising HDL cholesterol levels. The cardio-protective effect of alcohol is now not thought to vary by beverage type. In fact, evidence for an additional cardio-protective effect of antioxidant polyphenols in red wine is weak. The study of genetics variants of the alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) genes involved in alcohol metabolism is important to understand the patterns of drinking habits and its effects in stroke susceptibility. The enzyme alcohol dehydrogenase (ADH), which oxidizes alcohol to acetaldehyde, has proven to play an important role in alcohol metabolism. Seven genes encoding ADH are found in a tight cluster on chromosome 4 and some are polymorphic in white European populations. More active variants of ADH cause higher concentrations of acetaldehyde in the body following alcohol consumption and are therefore protective against drinking. Functional variants in both ADH1B and ADH1C have been associated with alcohol consumption or alcohol dependence. The ADH1B variant (rs1229984) has emerged as the most strongly associated with alcohol phenotypes and is therefore the most suitable instrument for Mendelian randomization studies in Europeans. The A allele has an allele frequency of approximately 2-5% in Europeans and plays a protective role against heavy drinking because it confers an higher alcohol metabolic rate and consequent accumulation of toxic acetaldehyde.