Examinando por Autor "Skowronska, Marta"

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  • Publicación
    Restringido
    Mendelian Genes and Risk of Intracerebral Hemorrhage and Small-Vessel Ischemic Stroke in Sporadic Cases
    (2017-08) Lopez-Jaramillo, Patricio; Chong, Michael; O’Donnell, Martin J.; Thijs, Vincent; Dans, Antonio; Gómez Arbeláez, Diego; Mondo, Charles; Czlonkowska, Anna; Skowronska, Marta; Oveisgharan, Shahram; Yusuf, Salim; Paré, Guillaume
    Background and Purpose—Mendelian strokes are rare genetic disorders characterized by early-onset small-vessel stroke. Although extensively studied among families with syndromic features, whether these genes affect risk among sporadic cases is unknown. Methods—We sequenced 8 genes responsible for Mendelian stroke in a case–control study of sporadic stroke cases (≤70 years). Participants included 1251 primary stroke cases of small-vessel pathology (637 intracerebral hemorrhage and 614 small-vessel ischemic stroke cases) and 1716 controls from the INTERSTROKE study (Study of the Importance of Conventional and Emerging Risk Factors of Stroke in Different Regions and Ethnic Groups of the World). Results—Overall, the prevalence of canonical disease-causing mutations was 0.56% in cases and 0.23% in controls (odds ratio=1.89; 95% confidence interval, 0.54–7.57; P=0.33). CADASIL (Cerebral Autosomal Dominant Arteriopathies with Subcortical Infarcts and Leukoencephalopathies) mutations were more frequent among cases (0.48%) than controls (0.23%) but were not significantly associated with stroke risk (odds ratio=2.03; 95% confidence interval, 0.58–8.02; P=0.27). Next, we included all rare nonsynonymous mutations to investigate whether other types of mutations may contribute to stroke risk. Overall, 13.5% of cases and 14.2% of controls were carriers of at least one rare nonsynonymous mutation among the 8 Mendelian stroke genes. Mutation carriers were not at elevated risk of stroke (odds ratio=0.93; 95% confidence interval, 0.75–1.16; P=0.55). Conclusions—In the absence of syndromic features and family history of stroke, screening for Mendelian mutations among small-vessel stroke patients is unlikely to have high diagnostic utility.
  • Publicación
    Restringido
    Peripheral Blood MCEMP1 Gene Expression as a Biomarker for Stroke Prognosis
    (2016-01-12) Lopez-Jaramillo, Patricio; Raman, Kripa; O’Donnell, Martin J.; Czlonkowska, Anna; Duarte, Yan Carlos; Peñaherrera, Ernesto; Sharma, Mike; Shoamanesh, Ashkan; Skowronska, Marta; Yusuf, Salim; Paré, Guillaume
    Background and Purpose—A limitation when making early decisions on stroke management is the lack of rapid diagnostic and prognostic testing. Our study sought to identify peripheral blood RNA biomarkers associated with stroke. The secondary aims were to assess the discriminative capacity of RNA biomarkers for primary stroke type and stroke prognosis at 1-month. Methods—Whole-blood gene expression profiling was conducted on the discovery cohort: 129 first-time stroke cases that had blood sampling within 5 days of symptom onset and 170 control participants with no history of stroke. Results—Through multiple regression analysis, we determined that expression of the gene MCEMP1 had the strongest association with stroke of 11181 genes tested. MCEMP1 increased by 2.4-fold in stroke when compared with controls (95% confidence interval, 2.0–2.8; P=8.2×10−22). In addition, expression was elevated in intracerebral hemorrhage when compared with ischemic stroke cases (P=3.9×10−4). MCEMP1 was also highest soon after symptom onset and had no association with stroke risk factors. Furthermore, MCEMP1 expression independently improved discrimination of 1-month outcome. Indeed, discrimination models for disability and mortality that included MCEMP1 expression, baseline modified Rankin Scale score, and primary stroke type improved discrimination when compared with a model without MCEMP1 (disability Net Reclassification Index, 0.76; P=3.0×10−6 and mortality Net Reclassification Index, 1.3; P=1.1×10−9). Significant associations with MCEMP1 were confirmed in an independent validation cohort of 28 stroke cases and 34 controls. Conclusions—This study demonstrates that peripheral blood expression of MCEMP1 may have utility for stroke diagnosis and as a prognostic biomarker of stroke outcome at 1-month.