Alexandre C Pereira

Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, San Paulo, São Paulo, Brazil

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Publications (159)651.29 Total impact

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    ABSTRACT: There is little information about how much traditional cardiovascular risk factors explain common carotid artery intima-media thickness (CCA-IMT) variance. We aimed to study to which extent CCA-IMT values are determined by traditional risk factors and which commonly used measurements of blood pressure, glucose metabolism, lipid profile, and adiposity contribute the most to this determination in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) baseline cohort. We analyzed 9792 individuals with complete data and CCA-IMT measurements. We built multiple linear regression models using mean left and right CCA-IMT as the dependent variable. All models were stratified by sex. We also analyzed individuals stratified by 10-year coronary heart disease risk and, in separate, those with no traditional risk factors. Main models' R(2) varied between 0.141 and 0.373. The major part of the explained variance in CCA-IMT was because of age and race. Indicators of blood pressure, lipid profile, and adiposity that most frequently composed the best models were pulse pressure, low-density lipoprotein/high-density lipoprotein ratio, and neck circumference. The association between neck circumference and CCA-IMT persisted significant even after further adjustment for vessel sizes and body mass index. Indicators of glucose metabolism had smaller contribution. We found that >60% of CCA-IMT were not explained by demographic and traditional cardiovascular risk factors, which highlights the need to study novel risk factors. Pulse pressure, low-density lipoprotein/high-density lipoprotein ratio, and neck circumference were the most consistent contributors. © 2015 American Heart Association, Inc.
    Arteriosclerosis Thrombosis and Vascular Biology 07/2015; DOI:10.1161/ATVBAHA.115.305765 · 5.53 Impact Factor
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    ABSTRACT: Familial hypercholesterolemia is characterized by elevated plasma cholesterol and early coronary arterial disease onset. However, few studies investigated the association of heterozygous familial hypercholesterolemia with peripheral arterial disease. In a cross sectional study 202 heterozygous familial hypercholesterolemia patients (91% confirmed by molecular diagnosis) were compared to 524 normolipidemic controls. Peripheral arterial disease was diagnosed by ankle-brachial index values ≤0.90. Compared with controls, familial hypercholesterolemia patients were older, more often female, with higher rates of hypertension, diabetes, previous coronary disease and higher total cholesterol levels. Smoking (previous and former) was more common among controls. The prevalence of peripheral arterial disease was 17.3 and 2.3% respectively in familial hypercholesterolemia and controls (p < 0.001). Results persisted after matching familial hypercholesterolemia and controls by a propensity score. Regression analyses demonstrated that age (odds ratio- OR = 1.03 95% CI 1.00-1.05, p = 0.033), previous cardiovascular disease (OR = 3.12 CI 95% 1.56-6.25, p = 0.001) and familial hypercholesterolemia diagnosis (OR = 5.55 CI 95% 2.69-11.44, p< 0.001) were independently associated with peripheral arterial disease. Among familial hypercholesterolemia patients, age (OR 1.05, 95% CI 1.02-1.09, p = 0.005), intermittent claudication (OR 6.32, 95% CI 2.60-15.33, p< 0.001) and smoking (OR 2.44, 95% CI 1.08-5.52, p = 0.032) were associated with peripheral arterial disease. Peripheral arterial disease is more frequent in familial hypercholesterolemia than in normolipidemic subjects and it should routine screened in these individuals even if asymptomatic. However, its role as predictor of cardiovascular events needs to be ascertained prospectively. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Atherosclerosis 07/2015; 242(1):174-178. DOI:10.1016/j.atherosclerosis.2015.07.022 · 3.97 Impact Factor
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    ABSTRACT: Studies of complex human diseases and traits associated with candidate genes are potentially vulnerable to bias (confounding) due to population stratification and inbreeding, especially in admixed population. In GWAS, the principal components (PCs) method provides a global ancestry value per subject, allowing corrections for population stratification. However, these coefficients are typically estimated assuming unrelated individuals, and if family structure is present and ignored, such substructures may induce artifactual PCs. Extensions of the PCs method have been proposed by Konishi and Rao [Biometrika 1992;79:631-641], taking into account only siblings' relatedness, and by Oualkacha et al. [Stat Appl Genet Mol Biol 2012, DOI: 10.2202/1544-6115.1711], taking into account large pedigrees and high-dimensional phenotype data. In this work, we extend these methods to estimate the global individual ancestry coefficients from PCs derived from different variance component matrix estimators using SNPs from two simulated data sets and two real data sets: the GENOA sibship data consisting of European and African-American subjects and the Baependi Heart Study consisting of 80 extended Brazilian families, both with genotyping data from the Affymetrix 6.0 chip. Our results show that the family structure plays an important role in the estimation of the global individual ancestry value for extended pedigrees but not for sibships. © 2015 S. Karger AG, Basel.
    Human Heredity 07/2015; 80(1):1-11. DOI:10.1159/000381908 · 1.64 Impact Factor
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    ABSTRACT: While South Americans are underrepresented in human genomic diversity studies, Brazil has been a classical model for population genetics studies on admixture. We present the results of the EPIGEN Brazil Initiative, the most comprehensive up-to-date genomic analysis of any Latin-American population. A population-based genome-wide analysis of 6,487 individuals was performed in the context of worldwide genomic diversity to elucidate how ancestry, kinship, and inbreeding interact in three populations with different histories from the Northeast (African ancestry: 50%), Southeast, and South (both with European ancestry >70%) of Brazil. We showed that ancestry-positive assortative mating permeated Brazilian history. We traced European ancestry in the Southeast/South to a wider European/Middle Eastern region with respect to the Northeast, where ancestry seems restricted to Iberia. By developing an approximate Bayesian computation framework, we infer more recent European immigration to the Southeast/South than to the Northeast. Also, the observed low Native-American ancestry (6-8%) was mostly introduced in different regions of Brazil soon after the European Conquest. We broadened our understanding of the African diaspora, the major destination of which was Brazil, by revealing that Brazilians display two within-Africa ancestry components: one associated with non-Bantu/western Africans (more evident in the Northeast and African Americans) and one associated with Bantu/eastern Africans (more present in the Southeast/South). Furthermore, the whole-genome analysis of 30 individuals (42-fold deep coverage) shows that continental admixture rather than local post-Columbian history is the main and complex determinant of the individual amount of deleterious genotypes.
    Proceedings of the National Academy of Sciences 06/2015; DOI:10.1073/pnas.1504447112 · 9.81 Impact Factor
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    ABSTRACT: Obstructive sleep apnea (OSA) has a familial aggregation pattern indicating that it can be partially caused by a genetic component. However, the heritability of OSA has been estimated based on the study of families of obese probands of urban populations with established OSA diagnosis. The objective of this genetic-epidemiologic study is to study families ascertained from a general rural population in order to determine an unbiased estimate of OSA heritability. We studied a sample of families living in Baependi, a small rural Southeastern Brazilian city. Participants were assessed for anthropometric measurements, physical examination, Epworth Sleepiness Scale, blood samples for glucose and cholesterol determination and overnight home portable monitoring (Stardust II). We studied 587 participants (399 women) from 91 families with a median (interquartile range) of 4 (2-8) participants per family. The median age of the population was 44 (29-55) years and body mass index (BMI) was 25.0 (22.1 - 28.6) kg/m2. OSA was defined Apnea Hypopnea Index (AHI) >15 events/h was diagnosed in 18.6% of the sample. Two polygenic models, model I (no covariate effects) and model II (with covariate effects) were fitted to the data in all analysis. Heritability estimates for AHI were 0.23 and 0.25 for model I and II, respectively. Covariates (age, sex and BMI) showed no significant effects on the heritability estimate for AHI. The heritability of AHI in a rural population with low levels of obesity is intermediate (25%).
    Chest 06/2015; DOI:10.1378/chest.15-0843 · 7.13 Impact Factor
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    ABSTRACT: In inherited cardiomyopathies, the investigation of genetics is recognized as an enriching procedure in the diagnostic closure of a cardiac condition. Many genetic mutations have been described as pathogenically related to cardiomyopathies, turning next-generation sequencing into an extremely reliable scenario. Here we describe the validation process of a pipeline constructed with a target panel of 74 cardiomyopathy-related genes sequenced using a next-generation sequencing system. Fifty-two samples from a hypertrophic cardiomyopathy casuistic with previous molecular diagnostics (Sanger-sequenced for MYH7, MYBCP3, and TNNT2; 19 positives and 33 negatives) were processed in parallel with a HapMap reference sample (NA12878) applied for a complete panel assessment. Sequencing coverage values were satisfactory, with a mean of 250× (95% CI, 226.03-273.91) and 95.2% of target bases with a coverage of ≥10×. With a total of 567 variants, variant call sensitivity was tested in five scenarios of coverage and variant allele frequency cutoffs. Maximum achieved sensitivity was 96.7% for single-nucleotide variants and 28.5% for indels, and positive predictive values remained above 0.959 during the whole process. Inter- and intra-assay reproducibility values were 89.5% and 87.3%, respectively. After a careful assessment of analytical performance, we infer that the assay presents potential feasibility for application in diagnostic routines, with minimal time requirements and a simple bioinformatics structure. Copyright © 2015 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.
    The Journal of molecular diagnostics: JMD 04/2015; DOI:10.1016/j.jmoldx.2015.02.003 · 3.96 Impact Factor
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    ABSTRACT: Noonan syndrome is an autosomal dominant, multisystemic disorder caused by dysregulation of the RAS/mitogen activated protein kinase (MAPK) pathway. Heterozygous, pathogenic variants in 11 known genes account for approximately 80% of cases. The identification of novel genes associated with Noonan syndrome has become increasingly challenging, since they might be responsible for very small fractions of the cases. A cohort of 50 Brazilian probands negative for pathogenic variants in the known genes associated with Noonan syndrome was tested through whole-exome sequencing along with the relatives in the familial cases. Families from the USA and Poland with mutations in the newly identified genes were included subsequently. We identified rare, segregating or de novo missense variants in SOS2 and LZTR1 in 4% and 8%, respectively, of the 50 Brazilian probands. SOS2 and LZTR1 variants were also found to segregate in one American and one Polish family. Notably, SOS2 variants were identified in patients with marked ectodermal involvement, similar to patients with SOS1 mutations. We identified two novel genes, SOS2 and LZTR1, associated with Noonan syndrome, thereby expanding the molecular spectrum of RASopathies. Mutations in these genes are responsible for approximately 3% of all patients with Noonan syndrome. While SOS2 is a natural candidate, because of its homology with SOS1, the functional role of LZTR1 in the RAS/MAPK pathway is not known, and it could not have been identified without the large pedigrees. Additional functional studies are needed to elucidate the role of LZTR1 in RAS/MAPK signalling and in the pathogenesis of Noonan syndrome. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Journal of Medical Genetics 03/2015; 52(6). DOI:10.1136/jmedgenet-2015-103018 · 5.64 Impact Factor
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    ABSTRACT: Diurnal preference (chronotype) is a useful instrument for studying circadian biology in humans. It harbours trait-like dimensions relating to circadian period and sleep homeostasis, but also has ontogenetic components (morningness increases with age). We used the Morningness-Eveningness questionnaire (MEQ) in the Baependi study, a family-based cohort study based in a small town in Minas Gerais, Brazil. The population is highly admixed and has a cohesive and conservative lifestyle. 825 individuals (497 female) aged 18-89 years (average ± SD = 46.4 ± 16.3) and belonging to 112 different families participated in this study. The average MEQ score was 63.5 ± 11.2 with a significant (P < 0.0001) linear increase with age. Morningness was significantly (P < 0.0001) higher in the rural (70.2 ± 9.8) than in the municipal zone (62.6 ± 11.1), and was also significantly (P = 0.025) higher in male (64.6 ± 10.9) than in female (62.8 ± 11.2) participants. Thus, in spite of universal access to electricity, the Baependi population was strongly shifted towards morningness, particularly in the rural zone. Heritability of MEQ score was 0.48 when adjusted for sex and age, or 0.38 when adjusted for sex, age, and residential zone. The reported MEQ score heritability is more akin to those of previous twin studies than previous family studies.
    Scientific Reports 03/2015; 5:9214. DOI:10.1038/srep09214 · 5.58 Impact Factor
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    ABSTRACT: The large individual variability in response to drugs for smoking cessation suggests that specific treatments can be more effective in particular subgroups of smokers. In the context of personalized medicine, the main aim of the present study was to evaluate whether the CHRNA4 and CHRNB2 polymorphisms are associated with response to smoking cessation therapies in patients from a smoker assistance program. This cohort study enrolled 483 smoking patients who received behavioral counseling and drug treatment (varenicline, bupropion, and/or nicotine replacement therapy). Smoking cessation success was considered for patients who completed 6 months of continuous abstinence. Fagerström test for nicotine dependence (FTND) and Issa situational smoking scores were analyzed for nicotine dependence. The CHRNA4 (rs1044396 and rs2236196) and CHRNB2 (rs2072660 and rs2072661) polymorphisms were genotyped by high resolution melting analysis. Patients with rs1044396 CC genotype had lower success rate in treatment with varenicline (29.5%) compared with carriers of CT or TT genotypes (50.9%; p = 0.007, n = 167). The CT or TT genotypes were associated with higher odds ratio for success (OR = 1.67, 95% CI = 1.10-2.53, p = 0.02), in a multivariate model. We did not observe significant differences in the FTND and Issa scores according to the studied polymorphisms. The CHRNA4 rs1044396 is associated with smoking cessation in individuals on varenicline therapy. We suggest that this polymorphism influences the varenicline response, but replications of this finding are needed.
    Frontiers in Genetics 02/2015; 6:46. DOI:10.3389/fgene.2015.00046
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    ABSTRACT: The association between functional β2 adrenergic receptor (β2-AR) polymorphisms and cardiac autonomic modulation is still unclear. Thus, two common polymorphisms in the β2-AR gene (Gln27Glu β2 and Arg16Gly β2) were studied to determine whether they might affect tonic and reflex cardiac sympathetic activity in healthy young subjects. A total of 213 healthy young white subjects of both genders (53% female), aged 18-30 years (23.5±3.4 y), had their continuous blood pressure curves noninvasively recorded by Finometer at baseline, and other hemodynamic parameters, as cardiac autonomic modulation, baroreflex sensitivity, and allele, genotype, and diplotype frequencies calculated. Associations were made between Arg16Gly β2 and Gln27Glu β2 polymorphisms and between β2-AR diplotypes and all variables. The heart rate was significantly lower (P<0.001) in the presence of homozygous Arg/Arg alleles (60.9±1.5 bpm) than in that of Arg/Gly heterozygotes (65.9±1.0 bpm) or Gly/Gly homozygotes (66.3±1.2 bpm). Homozygous carriers of Arg16 allele had an alpha index (19.2±1.3) significantly higher (P<0.001) than that of the subjects with the Gly allele Gly/Gly (14.5±0.7) or Arg/Gly (14.6±0.7). Furthermore, the recessive Glu27Glu and the heterozygous Gln27Glu genotypes had a higher percentage of low-frequency components (LF%) than the homozygous Gln27Gln (15.1% vs. 16.0% vs. 8.2%, P=0.03, respectively). In healthy young subjects, the presence of β2-AR Arg16 allele in a recessive model was associated with higher baroreflex sensitivity, and increased parasympathetic modulation in studied individuals.
    American Journal of Translational Research 01/2015; 7(1):153-61. · 3.23 Impact Factor
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    ABSTRACT: Background: There is little knowledge about familial hypercholesterolemia in Brazil. This study presents the first results of genetic cascade screening performed in the city of Sao Paulo. Material and methods: Two-hundred and forty-eight suspected index cases were initially included. DNA was extracted from peripheral blood and the complete coding sequence of low-density lipoprotein receptor, exon 7 of proprotein convertase subtilisin/kexin type 9 gene and part of exon 26 of apolipoprotein B genes were sequenced. Multiplex Ligation-dependent Probe Amplification was performed on cases where a causal mutation was not identified through sequencing. After the identification of a causal mutation screening in first-degree relatives was pursued. Results: From 248 index cases, a mutation was found in 125 individuals (50.4%). 394 relatives were included in the cascade screening program and a mutation was identified in 59.4%. Seventy different causal mutations in the low-density lipoprotein receptor gene (97.2%) and 2 in the apolipoprotein B gene (2.8%) were found. No mutations were encountered in the proprotein convertase subtilisin/kexin type 9 gene. Mutations in exons 14 and 4 were the most prevalent and, 10 cases of true homozygotes (8 index cases and 2 relatives) and 1 compound heterozygote were identified. The most frequent mutation found was of Lebanese origin, the p.(Cys681*) mutation in exon 14 (8.5%). Conclusion: Genetic familial hypercholesterolemia cascade screening is feasible in Brazil and leads to identification of a mutation in approximately half of the index cases with higher rates of success in their relatives. Copyright © 2014. Published by Elsevier Ireland Ltd.
    Atherosclerosis 11/2014; 238(1):101-107. DOI:10.1016/j.atherosclerosis.2014.11.009 · 3.97 Impact Factor
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    ABSTRACT: Noonan syndrome (NS) is an autosomal dominant disorder consisting of short stature, short and/or webbed neck, distinctive facial features, cardiac abnormalities, cryptorchidism, and coagulation defects. NS exhibits genetic heterogeneity, associated with mutated genes that participate in RAS-mitogen-activated protein kinase signal transduction. Recently, a new gene (RIT1) was discovered as the causative gene in 17 of 180 Japanese individuals who were negative for the previously known genes for NS and were studied using exome sequencing (four patients), followed by Sanger sequencing (13 patients). The present study used the same technique in 70 Brazilian patients with NS and identified six with RIT1 missense mutations. Thus, we confirm that RIT1 is responsible for approximately 10% of the patients negative for mutations in the previously known genes. The phenotype includes a high frequency of high birth weight, relative macrocephaly, left ventricular hypertrophy, and ectodermal findings, such as curly hair, hyperpigmentation, and wrinkled palms and soles. Short stature and pectus deformity were less frequent. The majority of patients with a RIT1 mutation did not show apparent intellectual disability. Because of the relatively high frequency of mutations in RIT1 among patients with NS and its occurrence in different populations, we suggest that it should be added to the list of genes included in panels for the molecular diagnosis of NS through targeted next-generation sequencing. © 2014 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part A 11/2014; 164(11). DOI:10.1002/ajmg.a.36722 · 2.05 Impact Factor
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    ABSTRACT: The frequency of resistant hypertension—defined as blood pressure (BP) ≥140/90 mm Hg with proven use of three antihypertensive medications, or as the use of four antihypertensive drug classes regardless of BP—is unknown in low-middle–income countries. Using data from the Brazilian Longitudinal Study of Adult Health, a cohort of 15,105 civil servants aged 35 to 74 years, the authors identified 4116 patients taking treatment for hypertension, 11% of who had resistant hypertension. These participants were more likely to be older, black, less educated, poorer, and obese. The adjusted prevalence ratios (95% confidence intervals) were diabetes, 1.44 (1.20–1.72); glomerular filtration rate (<60 mL/min/1.72 m2), 1.95 (1.60–2.38); albumin-to-creatinine ratio (>300 mg/g), 2.43 (1.70–3.50); carotid-femoral pulse-wave velocity, 1.07 m/s (1.03–1.11 m/s); common carotid intima-media thickness, 2.57 mm (1.64–4.00 mm); left ventricular hypertrophy, 2.08 (1.21–3.57); and atrial fibrillation, 3.55 (2.02–6.25). Thus, the prevalence of resistant hypertension in Brazil is high and associated with subclinical markers of end-organ cardiovascular damage.
    Journal of Clinical Hypertension 10/2014; 17(1). DOI:10.1111/jch.12433 · 2.96 Impact Factor
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    ABSTRACT: Funding Information This work was supported by Fundac ß~ ao Zerbini and Fundac ß~ ao de Amparo a Pesquisa (FAPESP 2011/04344-0). Abstract Several techniques to induce renal ischemia have been proposed: clamp, PVA particles, and catheter-balloon. We report the development of a controlled, single-insult model of unilateral renal ischemia/reperfusion (I/R) without contralateral nephrectomy, using a suitable model, the pig. This is a balloon-catheter-based model using a percutaneous, interventional radiology proce-dure. One angioplasty balloon-catheter was placed into the right renal artery and inflated for 120 min and reperfusion over 24 h. Serial serums were sam-pled from the inferior vena cava and urine was directly sampled from the bladder throughout the experiment, and both kidneys were excised after 24 h of reperfusion. Analyses of renal structure and function were performed by hematoxylin–eosin/periodic Acid-Schiff, serum creatinine (SCr), blood urea nitrogen (BUN), fractional excretion of ions, and glucose, SDS-PAGE analysis of urinary proteins, and serum neutrophil gelatinase-associated lipocalin (NGAL). Total nitrated protein was quantified to characterize oxidative stress. Acute tubular necrosis (ATN) was identified in every animal, but only two animals showed levels of SCr above 150% of baseline values. As expected, I/R increased SCr and BUN. Fractional sodium, potassium, chloride, and bicar-bonate excretion were modulated during ischemia. Serum-nitrated proteins and NGAL had two profiles: decreased with ischemia and increased after rep-erfusion. This decline was associated with increased protein excretion during ischemia and early reperfusion. Altogether, these data show that the renal I/R model can be performed by percutaneous approach in the swine model. This is a suitable translational model to study new early renal ischemic biomarkers and pathophysiological mechanisms in renal ischemia.
    09/2014; 2(9):e12150. DOI:10.14814/phy2.12150
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    ABSTRACT: Background A previous study reported that the myosin regulatory light chain interacting protein (MYLIP) might serve as a novel therapeutic class for treating dyslipidemia. It contributes to variations in the levels of circulating low-density lipoprotein cholesterol (LDL-C), promoting the degradation of LDL–LDLR, thus limiting absorption. The effect of genetic variation in the MYLIP gene in a disease scenario characterized by mutations in the LDLR gene has not been previously evaluated. Objective The aim of this study was to assess the effect of the p.N342S variant on the response to lipid-lowering therapy in Brazilian patients with heterozygous familial hypercholesterolemia (FH). Patients and methods A total of 156 patients with heterozygous FH were followed up for 12 months and received lipid-lowering therapy (different doses of atorvastatin with the addition of ezetimibe in over half the patients of each genotype group). Cholesterol data were assessed, and analysis of the MYLIP rs9370867 (p.N342S) genotypes was carried out by melting curve analysis. Results Baseline total cholesterol and baseline LDL-C levels were not different between genotypes. After 1 year of treatment, LDL-C responses (expressed as mg/dl and as %) were significantly different among genotypes (AA: −79±68 and −39±27, GA: −60±79 and −27±32, and GG: −30±83 and −15±38; P=0.02 and 0.005, respectively). In addition, FH patients carrying the AA genotype were more likely to achieve LDL-C levels of less than 130 mg/dl after 1 year of treatment (75.0%) compared with patients with the GG and GA genotypes (34.5 and 34.8%, respectively; P=0.001). Conclusion Our study indicates that MYLIP p.N342S might be a pharmacogenetic marker for lipid-lowering therapy in patients with FH.
    Pharmacogenetics and Genomics 08/2014; 24(11). DOI:10.1097/FPC.0000000000000089 · 3.45 Impact Factor
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    ABSTRACT: Increases in resting-state heart rate and decreases in its variability are associated with substantial morbidity and mortality, yet contradictory findings have been reported for the effects of the mood and anxiety disorders and of antidepressants. The authors investigated heart rate and heart rate variability in a large cohort from Brazil, using propensity score weighting, a relatively novel method, to control for numerous potential confounders.
    American Journal of Psychiatry 08/2014; DOI:10.1176/appi.ajp.2014.13121605 · 13.56 Impact Factor
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    International Journal of Cardiology 07/2014; 176(2). DOI:10.1016/j.ijcard.2014.07.039 · 6.18 Impact Factor
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    ABSTRACT: Objective The use of the anthropometric indices of adiposity, especially body mass index and waist circumference in the prediction of diabetes mellitus has been widely explored. Recently, a new body composition index, the body adiposity index was proposed. The aim of this study was to compare the effectiveness of body mass index, waist circumference, and body adiposity index in the risk assessment for type 2 diabetes mellitus. Design and methods A total of 1,572 individuals from the general population of Vitoria City, Brazil and 620 Amerindians from the Aracruz Indian Reserve, Brazil were randomly selected. BMI, waist circumference, and BAI were determined according to a standard protocol. Type 2 diabetes mellitus was diagnosed by the presence of fasting glucose ≥126 mg/dL or by the use of antidiabetic drugs. Results The area under the curve was similar for all anthropometric indices tested in the Amerindian population, but with very different sensitivities or specificities. In women from the general population, the area under the curve of waist circumference was significantly higher than that of the body adiposity index. Regarding risk assessment for type 2 diabetes mellitus, the body adiposity index was a better risk predictor than body mass index and waist circumference in the Amerindian population and was the index with highest odds ratio for type 2 diabetes mellitus in men from the general population, while in women from the general population waist circumference was the best risk predictor. Conclusion Body adiposity index was the best risk predictor for type 2 diabetes mellitus in the Amerindian population and men from the general population. Our data suggest that the body adiposity index is a useful tool for the risk assessment of type 2 diabetes mellitus in admixture populations.
    PLoS ONE 06/2014; 9(6):e100223. DOI:10.1371/journal.pone.0100223 · 3.53 Impact Factor
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    ABSTRACT: Abstract Effective analytical tools are highly desirable for data analysis and for making the biological link between genotypic and phenotypic measures. In family data it is important to reconcile the methods that explain the phenotypic variability through fixed genetic effects and ones that estimate variance components using classical heritability methods. Thus, in this paper, we propose a method based on added-variable plot for polygenic linear mixed models applied to genome wide association studies in family-based designs. Our goal is to be able to discriminate genetic predictor variables in effects due to random polygenic and residual components. We also propose an index to detect influential families for each predictor variable identified with genetic effect. We assess the performance of our proposed method using our own family simulated data and the Genetic Analysis Workshop 17 family simulated data.
    Statistical Applications in Genetics and Molecular Biology 06/2014; 13(3):359-78. DOI:10.1515/sagmb-2013-0057 · 1.52 Impact Factor

Publication Stats

2k Citations
651.29 Total Impact Points

Institutions

  • 2011–2015
    • Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
      • Instituto da Criança (ICr)
      San Paulo, São Paulo, Brazil
    • Universidade Federal de São Paulo
      San Paulo, São Paulo, Brazil
  • 2004–2015
    • Instituto do Coração
      San Paulo, São Paulo, Brazil
    • Brigham and Women's Hospital
      • Department of Medicine
      Boston, Massachusetts, United States
  • 1998–2015
    • University of São Paulo
      • • Faculty of Medicine (FM)
      • • Hospital das Clínicas (FMUSP)
      San Paulo, São Paulo, Brazil
  • 2012
    • Universidade Estácio de Sá
      Rio de Janeiro, Rio de Janeiro, Brazil
  • 2007–2012
    • Texas Heart Institute
      Houston, Texas, United States
    • Universidade Federal do Espírito Santo
      • Departamento de Ciências Fisiológicas
      Victoria, Espírito Santo, Brazil