Papers by Ana Isabel Freitas
European Heart Journal, 2020
Background Increasing evidence points epicardial adipose tissue (EAT) as an emerging cardiovascul... more Background Increasing evidence points epicardial adipose tissue (EAT) as an emerging cardiovascular risk marker. Whether genetic polymorphisms are associated with a higher EAT burden is still unknow. Genetic risk score (GRS) is an emerging method that attempts to establish correlation between single nucleotide polymorphisms (SNPs) and clinical phenotypes. Aim Evaluate the role of genetic burden and its association to EAT. Methods 996 patients (mean age 59±8, 78% male) were prospectively enrolled in a single center. EAT was measured on cardiac CT using a modified simplified method. Patients were divided into 2 groups (above vs. below the median EAT volume). We studied different polymorphisms across the following gene-regulated pathways: oxidation, renin-angiotensin system, cellular, diabetes/obesity and dyslipidemia pathways. Genotyping was performed by TaqMan allelic discrimination assay. A multiplicative genetic risk score (mGRS) was constructed and represents the genetic burden of...
Antioxidants (Basel, Switzerland), Jan 21, 2017
It has long been accepted that mitochondrial function and morphology is affected in Parkinson'... more It has long been accepted that mitochondrial function and morphology is affected in Parkinson's disease, and that mitochondrial function can be directly related to its morphology. So far, mitochondrial morphological alterations studies, in the context of this neurodegenerative disease, have been performed through microscopic methodologies. The goal of the present work is to address if the modifications in the mitochondrial-shaping proteins occurring in this disorder have implications in other cellular pathways, which might constitute important pathways for the disease progression. To do so, we conducted a novel approach through a thorough exploration of the available proteomics-based studies in the context of Parkinson's disease. The analysis provided insight into the altered biological pathways affected by changes in the expression of mitochondrial-shaping proteins via different bioinformatic tools. Unexpectedly, we observed that the mitochondrial-shaping proteins altered i...
Medicine, 2017
Essential hypertension (EH) is a complex disease in which physiological, environmental, and genet... more Essential hypertension (EH) is a complex disease in which physiological, environmental, and genetic factors are involved in its genesis. The genetic variant of the alpha-adducin gene (ADD1) has been described as a risk factor for EH, but with controversial results.The objective of this study was to evaluate the association of ADD1 (Gly460Trp) gene polymorphism with the EH risk in a population from Madeira Island.A case-control study with 1614 individuals of Caucasian origin was performed, including 817 individuals with EH and 797 controls. Cases and controls were matched for sex and age, by frequency-matching method. All participants collected blood for biochemical and genotypic analysis for the Gly460Trp polymorphism. We further investigated which variables were independently associated to EH, and, consequently, analyzed their interactions.In our study, we found a significant association between the ADD1 gene polymorphism and EH (odds ratio 2.484, P = .01). This association remaine...
Atherosclerosis, Mar 22, 2017
Conventional coronary artery disease (CAD) risk factors like age, gender, blood lipids, hypertens... more Conventional coronary artery disease (CAD) risk factors like age, gender, blood lipids, hypertension and smoking have been the basis of CAD risk prediction algorithms, but provide only modest discrimination. Genetic risk score (GRS) may provide improved discrimination over and above conventional risk factors. Here we analyzed the genetic risk of CAD in subjects from Pakistan, using a GRS of 21 variants in 18 genes and examined whether the GRS is associated with blood lipid levels. 625 (405 cases and 220 controls) subjects were genotyped for variants, NOS3 rs1799983, SMAD3 rs17228212, APOB rs1042031, LPA rs3798220, LPA rs10455872, SORT1 rs646776, APOE rs429358, GLUL rs10911021, FTO rs9939609, MIA3 rs17465637, CDKN2Ars10757274, DAB2IP rs7025486, CXCL12 rs1746048, ACE rs4341, APOA5 rs662799, CETP rs708272, MRAS rs9818870, LPL rs328, LPL rs1801177, PCSK9 rs11591147 and APOE rs7412 by TaqMan and KASPar allele discrimination techniques. Individually, the single SNPs were not associated wi...
Physiological Genomics, 2016
Recent genetic studies have revealed an association between polymorphisms at the ADAMTS7 gene loc... more Recent genetic studies have revealed an association between polymorphisms at the ADAMTS7 gene locus and coronary artery disease (CAD) risk. Functional studies have shown that a CAD-associated polymorphism (rs3825807) affects ADAMTS7 maturation and vascular smooth muscular cell (VSMC) migration. Here, we tested whether ADAMTS7 (A/G) SNP is associated with cardiovascular (CV) survival in patients with established CAD. A cohort of 1,128 patients with angiographic proven CAD, who were followed up prospectively for a mean follow-up period of 63 (range 6–182) mo, were genotyped for rs3825807 A/G. Survival statistics (Cox regression) compared heterozygous (AG) and wild-type (AA) with the reference homozygous GG. Kaplan-Meier (K-M) survival curves were performed according to ADAMTS7 genotypes for CV mortality. Results showed that 47.3% of patients were heterozygous (AG), 36.5% were homozygous for the wild-type allele (AA) and only 16.2% were homozygous for the GG genotype. During the follow...
Apidologie, 2015
Although the mitochondrial molecule of the honey bee is completely sequenced, the control region ... more Although the mitochondrial molecule of the honey bee is completely sequenced, the control region is rarely used for genetic inferences as in other invertebrates, due to several constraints mainly a biased A plus T content and extensive variable length repeats. Herein, we have analyzed the control region of honey bees from the Iberian Peninsula and North Atlantic islands. The information retrieved when comparing individuals from different populations was crucial to understand and characterize how the control region is organized in this species. As expected, this region in Apis mellifera appears to contain valuable although limited genetic information at the population level. Furthermore, the comparisons of the A. mellifera control region with other species of the same genus highlight the structural role of particular sequences within the A+T rich control region as proposed here.
Human molecular genetics, 2015
The physiological function of Ataxin-3 (ATXN3), a deubiquitylase (DUB) involved in Machado-Joseph... more The physiological function of Ataxin-3 (ATXN3), a deubiquitylase (DUB) involved in Machado-Joseph Disease (MJD), remains elusive. In this study, we demonstrate that ATXN3 is required for neuronal differentiation and for normal cell morphology, cytoskeletal organization, proliferation and survival of SH-SY5Y and PC12 cells. This cellular phenotype is associated with increased proteasomal degradation of α5 integrin subunit (ITGA5) and reduced activation of integrin signalling and is rescued by ITGA5 overexpression. Interestingly, silencing of ATXN3, overexpression of mutant versions of ATXN3 lacking catalytic activity or bearing an expanded polyglutamine (polyQ) tract led to partially overlapping phenotypes. In vivo analysis showed that both Atxn3 knockout and MJD transgenic mice had decreased levels of ITGA5 in the brain. Furthermore, abnormal morphology and reduced branching were observed both in cultured neurons expressing shRNA for ATXN3 and in those obtained from MJD mice. Our re...
Diabetologia, 2004
Aims/hypothesis. Gestational diabetes mellitus is a heterogeneous disorder characterised by impai... more Aims/hypothesis. Gestational diabetes mellitus is a heterogeneous disorder characterised by impaired insulin secretion and action. Our aim was to study whether autoimmunity, variations in genes affecting insulin secretion and action, or both, contribute to the development of gestational diabetes and whether the pathogenesis of the disease differs between women with a Scandinavian or Arabian background. Methods. We studied a total of 500 unrelated women with gestational diabetes (400 Scandinavian and 100 Arabian) and 550 unrelated pregnant non-diabetic control women (428 Scandinavian and 122 Arabian) matched for ethnicity. Results. Arabian women with gestational diabetes were 50% more insulin resistant for the same BMI compared with Scandinavian women with the disease (homeostasis model assessment [HOMA-IR]; 3.2±0.3 vs 2.2±0.2, p=0.02). Both Scandinavian (4.2% vs 0.9%, p=0.008) and Arabian (4.6% vs 0.0%, p=0.03) women with gestational diabetes had a higher frequency of GAD antibodies (GAD65Ab) than the matched controls. The frequency of HLA-DQB1 risk genotypes was slightly higher in Scandinavian women with gestational diabetes than in the Scandinavian controls (46.3% vs 38.8%, p=0.03) but no significant difference was found between the Arabian women with gestational diabetes and the Arabian controls (47% vs 51.6%, p=0.47). There were no significant differences in the frequency of the insulin gene variable number of tandem repeat (INS VNTR) alleles and genotypes or the peroxisome proliferator-activated receptor-gamma 2 (PPARγ2-Pro12Ala) polymorphism between the women with gestational diabetes and the control women either in Arabian or in Scandinavian women. Conclusions/interpretation. Gestational diabetes mellitus was associated with the presence of GAD65Ab in both study groups. Scandinavian women with gestational diabetes may share some genetic features with Type 1 diabetes. In addition, Arabian women with gestational diabetes are more insulin resistant than Scandinavian women with gestational diabetes and with the same BMI.
The Journal of antimicrobial chemotherapy, Jan 29, 2015
SmqnrR does not equally regulate the expression of Smqnr in all S. maltophilia strains. The intri... more SmqnrR does not equally regulate the expression of Smqnr in all S. maltophilia strains. The intrinsic resistome has been defined as the set of determinants that contribute to the specific phenotype of susceptibility to antibiotics of a given bacterial species. 9 Our results indicate that the contribution to intrinsic resistance (and its regulation) of the elements of bacterial intrinsic resistome (as Smqnr) can be strain-specific. We should therefore be aware that a feature observed in a specific bacterial strain cannot necessarily be extrapolated to the remaining strains of the same species. More studies in other S. maltophilia strains will be required to decipher whether the differential effect observed in these two strains is a general issue or just an exception for one of the analysed isolates.
Processes
Madeira wine (MW) encompasses an unusual oxidative ageing process that makes it distinctive. Seve... more Madeira wine (MW) encompasses an unusual oxidative ageing process that makes it distinctive. Several metabolites have been related to its quality and safety, such as 5-hydroxymethylfurfural (HMF), furfural, sotolon, and ethyl carbamate (EC). These compounds were quantified over a three-year period to assess their formation rate according to the ageing procedure used: canteiro vs. estufagem. Estufagem, which includes thermal processing of young MWs, promoted greater HMF, furfural, and sotolon accumulation, especially in sweet wines, in which sotolon contributed significantly to aroma (odour active values up to 17.5). Tinta Negra revealed a higher predisposition to form EC while Malvasia and Sercial were less prone to its formation. The formation of furfural, HMF, and EC strongly correlated with the ageing time. Sotolon had a strong correlation with the ageing time in canteiro (r = 0.79) and a moderate correlation in estufagem (r = 0.65). In both ageing procedures, sotolon, furfural, ...
Genetics and Molecular Biology, 2018
The utility of genetic risk scores (GRS) as independent risk predictors remains inconclusive. Her... more The utility of genetic risk scores (GRS) as independent risk predictors remains inconclusive. Here, we evaluate the additive value of a multi-locus GRS to the Framingham risk score (FRS) in coronary artery disease (CAD) risk prediction. A total of 2888 individuals (1566 coronary patients and 1322 controls) were divided into three subgroups according to FRS. Multiplicative GRS was determined for 32 genetic variants associated to CAD. Logistic Regression and Area Under the Curve (AUC) were determined first, using the TRF for each FRS subgroup, and secondly, adding GRS. Different models (TRF, TRF+GRS) were used to classify the subjects into risk categories for the FRS 10-year predicted risk. The improvement offered by GRS was expressed as Net Reclassification Index and Integrated Discrimination Improvement. Multivariate analysis showed that GRS was an independent predictor for CAD (OR = 1.87; p<0.0001). Diabetes, arterial hypertension, dyslipidemia and smoking status were also independent CAD predictors (p<0.05). GRS added predictive value to TRF across all risk subgroups. NRI showed a significant improvement in all categories. In conclusion, GRS provided a better incremental value in intermediate subgroup. In this subgroup, inclusion of genotyping may be considered to better stratify cardiovascular risk.
Revista portuguesa de cardiologia : orgao oficial da Sociedade Portuguesa de Cardiologia = Portuguese journal of cardiology : an official journal of the Portuguese Society of Cardiology, Jun 28, 2018
Hypertension is an important public health problem, affecting about 25% of the adult population w... more Hypertension is an important public health problem, affecting about 25% of the adult population worldwide.1 Genetic and environmental factors contribute to its pathogenesis. The T allele of the C825T polymorphism of the beta 3 subunit of G protein (rs5443) leads to the production of a truncated variant that enhances intracellular signaling and may interfere with the regulation of blood pressure. This genetic variant has been described as a risk factor for hypertension, although study results are controversial. The objective of this study was to analyze the association of the C825T polymorphism of the GNB3 gene with the occurrence of hypertension in a Portuguese population from the Madeira archipelago. A case-control study was performed with 1641 Caucasian individuals (mean age 50.6±8.1 years), 848 with hypertension and 793 controls. Blood was collected from all participants for biochemical and genetic analysis, including genotyping of the C825T polymorphism. Logistic regression anal...
Food Bioscience, 2015
The research effort described here has focused on incorporation of Lactobacillus casei, in whey p... more The research effort described here has focused on incorporation of Lactobacillus casei, in whey protein matrices, in the presence of selected salty additives. Those matrices were produced via thermal processing of a combination of either ovine or bovine whey (or a mixture thereof) with ovine milk, and were inoculated (at 10%) with L. casei strain LAFTI L26; salt, salt and herbs, or salt and xanthan were further added to such matrices, which were then homogenized and stored at 7 ºC for up to 21 d. In general, viable cell numbers maintained or even increased throughout the storage period, irrespective of the type of salty additive considered. Partial depletion of lactose was detected, and concomitant production of lactic acid throughout the 21 d-period of storage; lower lactic acid concentrations were found in matrices containing salty additives. In matrices with xanthan (SX), the probiotic strain exhibited the lowest metabolic activity. Matrices SX were less soft and firmer than the others, by the end of storage, and were similar to matrices with herbs (SH). The incorporation of salty additives affected bacterial metabolism, in terms of glycolysis and proteolysis, which in turn had a significant impact on the development of textural properties.
Revista portuguesa de cardiologia : orgão oficial da Sociedade Portuguesa de Cardiologia = Portuguese journal of cardiology : an official journal of the Portuguese Society of Cardiology, 2009
Various studies have compared coronary artery disease (CAD) patients with controls in order to de... more Various studies have compared coronary artery disease (CAD) patients with controls in order to determine which polymorphisms are associated with a higher risk of disease. The results have often been contradictory. Moreover, these studies evaluated polymorphisms in isolation and not in association, which is the way they occur in nature. Our purpose was to evaluate the risk of CAD in patients with associated polymorphisms in the same gene or in differen genes. We evaluated the risk associated with ACE DD, ACE 8 CC, ACT 174MM, AGT 235TT, MTHFR 677TT, MTHFR 1298AA, PON1 192RR and PON1 55MM in 298 CAD patients and 298 healthy individuals. We then evaluated the risk of associated polymorphisms in the same gene (ACE DD + ACE 8GG; AGT 174MM + AGT 235TT; MTHFR 677TT + MTHFR 1298AA). Finally, for the isolated polymorphisms which were significant, we evaluated the risk of polymorphism associations at different functional levels (ACE + AGT; ACE + MTHFR; ACE + PON1). Multiple logistic regression...
Microevolutionary Events Involving Narrow Host Plasmids Influences Local Fixation of Vancomycin-Resistance in Enterococcus Populations
PLoS ONE, 2013
TrAC Trends in Analytical Chemistry, 2012
Functional foods (FFs) are food products to be consumed as part of a balanced diet. They provide ... more Functional foods (FFs) are food products to be consumed as part of a balanced diet. They provide physiological benefits or reduce the risk of chronic disease beyond basic nutritional functions. Functional foods containing probiotics and/or prebiotics have gained much interest in recent years due to their health-promoting capacity. The main objective of this review is to discuss the analytical strategies that have been used to validate FFs associated with dairy products containing probiotics and/or prebiotics. In these products, the biochemical events, carried out by enzymes of different sources (milk, bacteria, rennet) leading to the transformation of milk to diverse products (e.g., yoghurt and cheese), are glycolysis, proteolysis and lipolysis. We present the analytical methodologies used to study the microbial probiotic flora and to evaluate the biochemical transformations, the associated functionality in terms of intestinal microbiome and the safety of such FFs. We address the analytical figures of merit. We cover the advantages and the disadvantages of such analytical methodologies and comment on future applications and potential research interest within this field.
Thrombosis Research, 2008
Elevated levels of plasma homocysteine, an independent risk factor and a strong predictor of mort... more Elevated levels of plasma homocysteine, an independent risk factor and a strong predictor of mortality in patients with coronary artery disease (CAD), can result from nutritional deficiencies or genetic errors, including methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms. The contribution of these polymorphisms in the development of CAD remains controversial. We analysed the impact of MTHFR C677T and A1298C on fasting homocysteine and CAD in 298 CAD patients proved by angiography and 510 control subjects from the Island of Madeira (Portugal). After adjustment for other risk factors, plasma homocysteine remained independently correlated with CAD. Serum homocysteine was significantly higher in individuals with 677TT and 1298AA genotypes. There was no difference in the distribution of MTHFR677 genotypes between cases and controls but a significant increase in 1298AA prevalence was found in CAD patients. In spite of the clear effect of C677T mutation on elevated homocysteine levels we only found an association between 1298AA genotype and CAD in this population. The simultaneous presence of 677CT and 1298AA genotypes provides a significant risk of developing the disease, while the 1298AC genotype, combined with 677CC, shows a significant trend towards a decrease in CAD occurrence. The data shows an independent association between
Science of The Total Environment, 2013
• Strategies based on silica monoliths for removing chemical pollutants are reviewed. • Discussio... more • Strategies based on silica monoliths for removing chemical pollutants are reviewed. • Discussion of the application and potential interest of using composites and biocomposites based on silica monoliths. • The main studies carried out using composites and biocomposites are presented and discussed. • Composites/biocomposites have been revealed to be efficient for removal/degradation of specific chemical compounds. • Advantages and drawbacks of using silica monoliths for removing pollutants are summarized.
Human and Swine Hosts Share Vancomycin-Resistant Enterococcus faecium CC17 and CC5 and Enterococcus faecalis CC2 Clonal Clusters Harboring Tn 1546 on Indistinguishable Plasmids
Journal of Clinical Microbiology, 2011
VRE isolates from pigs ( n = 29) and healthy persons ( n = 12) recovered during wide surveillance... more VRE isolates from pigs ( n = 29) and healthy persons ( n = 12) recovered during wide surveillance studies performed in Portugal, Denmark, Spain, Switzerland, and the United States (1995 to 2008) were compared with outbreak/prevalent VRE clinical strains ( n = 190; 23 countries; 1986 to 2009). Thirty clonally related Enterococcus faecium clonal complex 5 (CC5) isolates (17 sequence type 6 [ST6], 6 ST5, 5 ST185, 1 ST147, and 1 ST493) were obtained from feces of swine and healthy humans. This collection included isolates widespread among pigs of European Union (EU) countries since the mid-1990s. Each ST comprised isolates showing similar pulsed-field gel electrophoresis (PFGE) patterns (≤6 bands difference; >82% similarity). Some CC5 PFGE subtype strains from swine were indistinguishable from hospital vancomycin-resistant enterococci (VRE) causing infections. A truncated variant of Tn 1546 (encoding resistance to vancomycin) and tcrB (coding for resistance to copper) were consistent...
Journal of Applied Microbiology, 2014
Aim: To evaluate the synergistic activity of antimicrobial drugs against lineages of methicillin-... more Aim: To evaluate the synergistic activity of antimicrobial drugs against lineages of methicillin-resistant Staphylococcus aureus (MRSA) carrying SCCmec IV. The biofilm production and related genes were also detected. Methods and Results: Forty two MRSA isolates were tested for biofilm production and related genes. Biofilm/biomass susceptibility to gentamicin (G), linezolid (L), rifampicin (R) and vancomycin (V) was determined for six isolates from three lineages prevalent in Rio de Janeiro hospitals in concentrations ranging from 0Á25 to 64 lg ml À1. Biomass was evaluated by microtitre plate test and number of viable cells (CFU cm À2) and inspected by epifluorescence microscopy. All isolates presented the icaA and sasG genes, but only 38% were biofilm producers. There were 50 and 45% biomass reductions when concentrations ≥4 lg ml À1 of R or L and ≥16 lg ml À1 of G or V, respectively, were used. Synergism tests produced a 55% biomass reduction with R 2lg ml À1 + G 16lg ml À1 , R 2lg ml À1 + L 2lg ml À1 , R 2lg ml À1 + V 4lg ml À1 , and L 2lg ml À1 + V 4lg ml À1. Number of viable cells was reduced from 2 to 3 logs with R 2lg ml À1 + L 2lg ml À1 and R 2lg ml À1 + V 4lg ml À1. Conclusions: Synergisms involving R plus L and R plus V caused important reductions in biofilm/biomass and the number of viable cells. Drug combinations should be considered in the chemotherapies of MRSA-SCCmec IV infections. Significance and Impact of the Study: Biofilms in MRSA infections restrict the clinical choice of antimicrobials. Thus, knowledge of the best options for monotherapy and drug synergisms could improve clinical results.
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Papers by Ana Isabel Freitas