Papers by Carolina Soriano
Neurology, 2018
Objective: We performed a genome-wide association study (GWAS) of ICH volume with the aims of ide... more Objective: We performed a genome-wide association study (GWAS) of ICH volume with the aims of identifying novel biological pathways involved in the pathophysiology of ICH. Background: Hematoma volume is a powerful predictor of clinical outcome in spontaneous intracerebral hemorrhage (ICH). Recent studies indicate that the role of genetic variation extends beyond risk to also influence clinical severity, radiological severity and functional outcome in this condition. Despite these findings, GWAS focused on ICH volume are lacking. Design/Methods: We conducted a two-stage (discovery and replication) cohort study that included ICH patients of European ancestry. We utilized admission head CT to calculate hematoma volume and classify ICH cases as lobar or non-lobar. Seven million genetic variants were available for association testing, which was carried out using linear regression. Signals with p −8 were pursued in replication and tested for association with admission Glasgow Coma Scale (...
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European Journal of Clinical Investigation, 2020
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Stroke, 2018
Hematoma volume is an important determinant of clinical outcome in spontaneous intracerebral hemo... more Hematoma volume is an important determinant of clinical outcome in spontaneous intracerebral hemorrhage (ICH). We performed a genome-wide association study (GWAS) of hematoma volume with the aim of identifying novel biological pathways involved in the pathophysiology of primary brain injury in ICH. We conducted a 2-stage (discovery and replication) case-only genome-wide association study in patients with ICH of European ancestry. We utilized the admission head computed tomography to calculate hematoma volume via semiautomated computer-assisted technique. After quality control and imputation, 7 million genetic variants were available for association testing with ICH volume, which was performed separately in lobar and nonlobar ICH cases using linear regression. Signals with <5×10 were pursued in replication and tested for association with admission Glasgow coma scale and 3-month post-ICH dichotomized (0-2 versus 3-6) modified Rankin Scale using ordinal and logistic regression, resp...
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European journal of Implant and Refractive Surgery, 1995
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The Lancet Neurology, 2016
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Annals of neurology, Nov 22, 2016
Objective In observational epidemiologic studies, higher plasma high-density lipoprotein choleste... more Objective In observational epidemiologic studies, higher plasma high-density lipoprotein cholesterol (HDL-C) has been associated with increased risk of intracerebral hemorrhage (ICH). DNA sequence variants that decrease cholesteryl ester transfer protein (CETP) gene activity increase plasma HDL-C; as such, medicines that inhibit CETP and raise HDL-C are in clinical development. Here, we test the hypothesis that CETP DNA sequence variants associated with higher HDL-C also increase risk for ICH. Methods We performed two candidate-gene analyses of CETP. First, we tested individual CETP variants in a discovery cohort of 1149 ICH cases and 1238 controls from 3 studies, followed by replication in 1625 cases and 1845 controls from 5 studies. Second, we constructed a genetic risk score comprised of 7 independent variants at the CETP locus and tested this score for association with HDL-C as well as ICH risk. Results Twelve variants within CETP demonstrated nominal association with ICH, with ...
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Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 2008
It has been well documented that long-term exposure to inorganic arsenic induces cancers and vasc... more It has been well documented that long-term exposure to inorganic arsenic induces cancers and vascular diseases in a dose-response relationship. Nevertheless, arsenic has also demonstrated to have anticancer activity; thus, arsenic trioxide (ATO, As2O3) is an inorganic trivalent arsenic form, currently used in the treatment against acute promyelocytic leukaemia (APL). The open discussion about how arsenic compounds induce genotoxic damage has moved us to evaluate the mutational spectrum induced by ATO in mouse lymphoma cells. Thus, 49 Tk-/- mutant colonies obtained in the mouse lymphoma assay (MLA), after treatments lasting for 4h with 10microM ATO, and 49 spontaneous mutant colonies from independent untreated cultures, were used to analyse and to characterise the mutational spectrum induced by this arsenic compound, to understand its mechanism of action. RT-PCR analysis of Tk cDNA and PCR amplifications of eight selected microsatellite sequences, located on chromosome 11, were used to carry out this screening. Our results show that, in mouse lymphoma cells, ATO is a strong clastogenic compound inducing large deletions, at chromosomal level, covering the Tk gene, as well as other regions of chromosome 11.
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PLoS ONE, 2014
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Stroke, 2012
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Neurología, 2014
ABSTRACT This article provides an overview of stroke genetics studies ranging from the candidate ... more ABSTRACT This article provides an overview of stroke genetics studies ranging from the candidate gene approach to more recent studies by the genome wide association. It highlights the complexity of stroke owing to its different aetiopathogenic mechanisms, the difficulties in studying its genetic component, and the solutions provided to date. The study emphasises the importance of cooperation between the different centres, whether this takes places occasionally or through the creation of lasting consortiums. This strategy is currently essential to the completion of high-quality scientific studies that allow researchers to gain a better knowledge of the genetic component of stroke as it relates to aetiology, treatment, and prevention.
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Stroke, 2013
Background and Purpose— Previous studies suggest that genetic variation plays a substantial role ... more Background and Purpose— Previous studies suggest that genetic variation plays a substantial role in occurrence and evolution of intracerebral hemorrhage (ICH). Genetic contribution to disease can be determined by calculating heritability using family-based data, but such an approach is impractical for ICH because of lack of large pedigree-based studies. However, a novel analytic tool based on genome-wide data allows heritability estimation from unrelated subjects. We sought to apply this method to provide heritability estimates for ICH risk, severity, and outcome. Methods— We analyzed genome-wide genotype data for 791 ICH cases and 876 controls, and determined heritability as the proportion of variation in phenotype attributable to captured genetic variants. Contribution to heritability was separately estimated for the APOE (encoding apolipoprotein E) gene, an established genetic risk factor, and for the rest of the genome. Analyzed phenotypes included ICH risk, admission hematoma v...
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PLoS ONE, 2014
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Neurology, 2013
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Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 2007
Arsenic compounds are generally considered as poor inducers of gene mutations. To investigate the... more Arsenic compounds are generally considered as poor inducers of gene mutations. To investigate the mutagenicity of several arsenic compounds at the thymidine kinase (Tk) gene, a reporter gene for mutation induction, we used the mouse lymphoma assay (MLA). This test is widely applied and detects a broad spectrum of mutational events, from point mutations to chromosome alterations. The selected arsenic compounds were two inorganic (sodium arsenite and arsenic trioxide) and four organic compounds (monomethylarsonic acid, dimethylarsinic acid, tetraphenylarsenium and arsenobetaine). The results show that sodium arsenite, arsenic trioxide, monomethylarsonic acid and dimethylarsinic acid are mutagenic, showing a clear dose-response pattern. On the other hand, tetraphenylarsenium and arsenobetaine are not mutagenic. Inorganic arsenic compounds are the more potent agents producing significant effects in the micromolar range, while the mutagenic organic arsenic compounds induce similar effects but in the millimolar range.
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Journal of Neurology, Neurosurgery & Psychiatry, 2012
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Food and Chemical Toxicology, 2010
Exposure of male (55.1 mg/kg b.wt. orally for 60 days) and/or pregnant female Wistar rats (55.1 m... more Exposure of male (55.1 mg/kg b.wt. orally for 60 days) and/or pregnant female Wistar rats (55.1 mg/kg b.wt. orally at days 6-15 of gestation), to the insecticide cypermethrin (CYP); resulted in the development of a lot of external morphological deformities and visceral malformations in their offspring pubs, which signify the potential of such insecticide to induce reproductive toxicity and teratogenesis. Data cleared that CYP treatment induced significant increase in the percentages of post-implantation deaths, dwarf foeti and subcutaneous oedema beside significant decrease in percentages of live borne foeti and uterine implants. CYP also caused many visceral malformations among different treated groups including nasal, ophthalmic, cerebral, pulmonary, cardiac and renal malformations. Concomitant oral administration of garlic extract or vitamin C (5 days/week) to treated fathers and/or pregnant mothers with CYP provided significant reduction in the percentage of the foetal malformations induced by the insecticide, when compared with the control. The current study proves that garlic and ascorbic acid dampen the reproductive toxicity and/or teratogenicity of cypermethrin toxicity in rats; therefore might prove to be effective dietary supplements in developing countries where pesticide pollution is high.
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European Journal of Neurology, 2012
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Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 2011
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Papers by Carolina Soriano