Alexandre C Pereira

Fundação Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil

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Publications (169)663.75 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Dyslipidemia is a pivotal risk factor for coronary heart disease (CHD). The purpose of this study was to identify the profile of dyslipidemia in a Brazilian population, according to high low-density lipoprotein (LDL-C) levels. We used the classification of the 2004 update of National Cholesterol Education Program Adult Treatment Panel III (ATP-III).
    No preview · Article · Jan 2016 · Journal of Clinical Lipidology
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    ABSTRACT: Background— Our goal was to evaluate cross-sectionally the association between ideal risk factors (IRF) profile and the presence and severity of subclinical atherosclerosis measured as coronary artery calcium (CAC) in the Brazilian Longitudinal Study of Adult Health. Methods—We included 4077 participants with no prior history of cardiovascular disease aged 35-74 years who underwent CAC measurement. The 2010 Task Force of the American Heart Association cut-offs were used to define the ideal level of smoking, physical activity, diet, blood pressure, glucose/cholesterol levels, and body-mass index. Results—Participants were categorized according the number of IRF: 0-1 (n=1025, 25.1%), 2 (n=1200, 29.4%), 3-4 (n=1551, 38.1%), or 5-7 (n=301, 7.4%). Compared to individuals with 0-1 IRF, the odds ratio (OR) of participants with 2 IRF presenting with CAC >0 (compared to 0), ≥100 (compared to <100), and ≥400 (compared to <400) was 0.75 (95% confidence interval [95%CI]: 0.62- 0.91), 0.64 (0.49-0.84), and 0.75 (0.49-1.15), respectively. Similarly, the ORs of CACs > 0, ≥100, and ≥400 in individuals with 3-4 IRF were 0.59 (95%CI: 0.48-0.71), 0.46 (0.34-0.62), and 0.50 (0.30-0.83), respectively; and for individuals with 5-7 IRF were 0.36 (95%CI: 0.24-0.56), 0.22 (0.09-0.55), and 0.20 (0.03-1.45), respectively. Conclusions— Subjects with an IRF profile have lower CAC when compared to subjects with fewer controlled risk factors. However, even among individuals with 5 to 7 IRF, it is possible to find a CAC higher than zero reflecting that measures of IRF do not fully account for all factors that resulted in coronary artery disease.
    No preview · Article · Jan 2016 · American Heart Journal
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    ABSTRACT: To investigate the phenotypic and genetic overlap between anxiety and depression symptoms in an admixed population from extended family pedigrees. Participants (n = 1,375) were recruited from a cohort of 93 families (mean age±SD 42±16.3, 57% female) in the rural town of Baependi, Brazil. The Hospital Anxiety and Depression Scale (HADS) was used to assess depression and anxiety symptoms. Heritability estimates were obtained by an adjusted variance component model. Bivariate analyses were performed to obtain the partition of the covariance of anxiety and depression into genetic and environmental components, and to calculate the genetic contribution modulating both sets of symptoms. Anxiety and depression scores were 7.49±4.01 and 5.70±3.82, respectively. Mean scores were affected by age and were significantly higher in women. Heritability for depression and anxiety, corrected for age and sex, were 0.30 and 0.32, respectively. Significant genetic correlations (ρg = 0.81) were found between anxiety and depression scores; thus, nearly 66% of the total genetic variance in one set of symptoms was shared with the other set. Our results provided strong evidence for a genetic overlap between anxiety and depression symptoms, which has relevance for our understanding of the biological basis of these constructs and could be exploited in genome-wide association studies.
    Full-text · Article · Dec 2015 · PLoS ONE
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    ABSTRACT: Asthma is a chronic disease of the airways and, despite the advances in the knowledge of associated genetic regions in recent years, their mechanisms have yet to be explored. Several genome-wide association studies have been carried out in recent years, but none of these have involved Latin American populations with a high level of miscegenation, as is seen in the Brazilian population. 1246 children were recruited from a longitudinal cohort study in Salvador, Brazil. Asthma symptoms were identified in accordance with an International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Following quality control, 1 877 526 autosomal SNPs were tested for association with childhood asthma symptoms by logistic regression using an additive genetic model. We complemented the analysis with an estimate of the phenotypic variance explained by common genetic variants. Replications were investigated in independent Mexican and US Latino samples. Two chromosomal regions reached genome-wide significance level for childhood asthma symptoms: the 14q11 region flanking the DAD1 and OXA1L genes (rs1999071, MAF 0.32, OR 1.78, 95 % CI 1.45–2.18, p-value 2.83 × 10 −8 ) and 15q22 region flanking the FOXB1 gene (rs10519031, MAF 0.04, OR 3.0, 95 % CI 2.02–4.49, p-value 6.68 × 10 −8 and rs8029377, MAF 0.03, OR 2.49, 95 % CI 1.76–3.53, p-value 2.45 × 10 −7 ). eQTL analysis suggests that rs1999071 regulates the expression of OXA1L gene. However, the original findings were not replicated in the Mexican or US Latino samples. We conclude that the 14q11 and 15q22 regions may be associated with asthma symptoms in childhood.
    Full-text · Article · Dec 2015 · BMC Genetics
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    ABSTRACT: Background and aims: Carotid artery intima-media thickness (CIMT) may be used as a biomarker for early cognitive impairment. However, the results of the association between CIMT and cognitive function in middle-aged subjects are mixed. We aimed to investigate this association in a large Brazilian sample with no history of stroke at baseline. Additionally, we tested the effect of interactions between CIMT and cardiovascular risk factors on cognitive performance. Methods: In this cross-sectional study, cognition was evaluated using the delayed word recall (DWRT), the category fluency, and the trail making tests (TMT). CIMT was measured at the common carotid artery. The association between CIMT and cognitive tests was investigated using linear regression models, adjusted for an extensive set of possible confounding variables. We also included interaction terms with selected risk factors. Results: The mean age of the 8208 participants was 49.6 ± 7.3 years, 44% were male, and 56% White. Increase in CIMT was associated with worse performance on the DWRT (β = -0.433, 95%CI = -0.724;-0.142, p = 0.004). We found effect modification of the association between cognitive function and CMIT by self-reported heart failure and alcohol intake. Participants had worse performance in the TMT if they had greater CIMT and current alcohol use (p < 0.0001). The interaction between CIMT and heart failure on TMT performance was not significant after adjustment for multiple comparisons (p = 0.07). Conclusions: In this sample of middle-aged adults, CIMT was inversely associated with memory function. Additionally, the presence of alcohol use resulted in a stronger association of CIMT with worse performance on an executive function test.
    No preview · Article · Oct 2015 · Atherosclerosis
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    ABSTRACT: The Brazilian population is considered to be highly admixed. The main contributing ancestral populations were European and African, with Amerindians contributing to a lesser extent. The aims of this study were to provide a resource for determining and quantifying individual continental ancestry using the smallest number of SNPs possible, thus allowing for a cost- and time-efficient strategy for genomic ancestry determination. We identified and validated a minimum set of 192 ancestry informative markers (AIMs) for the genetic ancestry determination of Brazilian populations. These markers were selected on the basis of their distribution throughout the human genome, and their capacity of being genotyped on widely available commercial platforms. We analyzed genotyping data from 6487 individuals belonging to three Brazilian cohorts. Estimates of individual admixture using this 192 AIM panels were highly correlated with estimates using ~370 000 genome-wide SNPs: 91%, 92%, and 74% of, respectively, African, European, and Native American ancestry components. Besides that, 192 AIMs are well distributed among populations from these ancestral continents, allowing greater freedom in future studies with this panel regarding the choice of reference populations. We also observed that genetic ancestry inferred by AIMs provides similar association results to the one obtained using ancestry inferred by genomic data (370 K SNPs) in a simple regression model with rs1426654, related to skin pigmentation, genotypes as dependent variable. In conclusion, these markers can be used to identify and accurately quantify ancestry of Latin Americans or US Hispanics/Latino individuals, in particular in the context of fine-mapping strategies that require the quantification of continental ancestry in thousands of individuals.European Journal of Human Genetics advance online publication, 23 September 2015; doi:10.1038/ejhg.2015.187.
    No preview · Article · Sep 2015 · European journal of human genetics: EJHG
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    Full-text · Dataset · Jul 2015
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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.
    Full-text · Article · Jul 2015 · Arteriosclerosis Thrombosis and Vascular Biology
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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.
    Full-text · Article · Jul 2015 · Atherosclerosis
  • Mariza de Andrade · Debashree Ray · Alexandre C Pereira · Júlia P Soler
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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.
    No preview · Article · Jul 2015 · Human Heredity
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    Full-text · Dataset · Jul 2015
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    ABSTRACT: Serum parathyroid hormone (PTH) has been found to be associated with cardiovascular mortality in the elderly, but little is known about the mechanisms underlying this association. This study investigated the association between PTH and structural and functional changes of the heart and arterial wall in a cohort of very elderly individuals. Healthy individuals aged 80 years or more (n = 90) underwent evaluation of serum PTH, cardiac morphology and function by Doppler echocardiography, endothelium dependent and independent vasodilatation by brachial reactivity, carotid stiffness and intima-media thickness by ultrasound, and coronary calcification by computed tomography. Participants with PTH levels above the median 5.8 pmol/L had higher left ventricular mass index (P = .02), relative wall thickness (P = .02), left atrial volume index (P = .03), and shorter deceleration time of E mitral wave (P = .04). Serum PTH levels (odds ratio, 1.027; P = .032) and systolic blood pressure (odds ratio, 1.032; P = .008) were independently associated with left ventricular hypertrophy. No difference was found between PTH groups in flow- or nitrate-mediated brachial artery dilatation, coronary artery calcification, intima-media thickness, or arterial stiffness. Elevation of serum PTH in the very elderly is associated with concentric left ventricular hypertrophy, but no association with arterial wall structure or function was found in this study. Copyright © 2015 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.
    No preview · Article · Jul 2015 · Journal of the American Society of Hypertension (JASH)
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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.
    Full-text · Article · Jun 2015 · Proceedings of the National Academy of Sciences
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    ABSTRACT: Diabetes has been defined on the basis of different biomarkers, including fasting plasma glucose (FPG), 2-h plasma glucose in an oral glucose tolerance test (2hOGTT), and HbA(1c). We assessed the effect of different diagnostic definitions on both the population prevalence of diabetes and the classification of previously undiagnosed individuals as having diabetes versus not having diabetes in a pooled analysis of data from population-based health examination surveys in different regions. Methods: We used data from 96 population-based health examination surveys that had measured at least two of the biomarkers used for defining diabetes. Diabetes was defined using HbA(1c) (HbA(1c) >= 6 . 5% or history of diabetes diagnosis or using insulin or oral hypoglycaemic drugs) compared with either FPG only or FPG-or-2hOGTT definitions (FPG >= 7 . 0 mmol/L or 2hOGTT >= 11 . 1 mmol/L or history of diabetes or using insulin or oral hypoglycaemic drugs). We calculated diabetes prevalence, taking into account complex survey design and survey sample weights. We compared the prevalences of diabetes using different definitions graphically and by regression analyses. We calculated sensitivity and specificity of diabetes diagnosis based on HbA1c compared with diagnosis based on glucose among previously undiagnosed individuals (ie, excluding those with history of diabetes or using insulin or oral hypoglycaemic drugs). We calculated sensitivity and specificity in each survey, and then pooled results using a random-effects model. We assessed the sources of heterogeneity of sensitivity by meta-regressions for study characteristics selected a priori. Findings: Population prevalence of diabetes based on FPG- or-2hOGTT was correlated with prevalence based on FPG alone (r= 0 . 98), but was higher by 2-6 percentage points at different prevalence levels. Prevalence based on HbA(1c) was lower than prevalence based on FPG in 42 . 8% of age-sex-survey groups and higher in another 41 . 6%; in the other 15 . 6%, the two definitions provided similar prevalence estimates. The variation across studies in the relation between glucose-based and HbA(1c)-based prevalences was partly related to participants' age, followed by natural logarithm of per person gross domestic product, the year of survey, mean BMI, and whether the survey population was national, subnational, or from specific communities. Diabetes defined as HbA(1c) 6 . 5% or more had a pooled sensitivity of 52 . 8% (95% CI 51 . 3-54 . 3%) and a pooled specificity of 99 . 74% (99 . 71-99 . 78%) compared with FPG 7 . 0 mmol/L or more for diagnosing previously undiagnosed participants; sensitivity compared with diabetes defined based on FPG-or-2hOGTT was 30 . 5% (28 . 7-32 . 3%). None of the preselected study-level characteristics explained the heterogeneity in the sensitivity of HbA(1c) versus FPG. Interpretation: Different biomarkers and definitions for diabetes can provide different estimates of population prevalence of diabetes, and differentially identify people without previous diagnosis as having diabetes. Using an HbA(1c)-based definition alone in health surveys will not identify a substantial proportion of previously undiagnosed people who would be considered as having diabetes using a glucose-based test.
    Full-text · Article · Jun 2015 · The Lancet Diabetes & Endocrinology
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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%).
    No preview · Article · Jun 2015 · Chest
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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.
    No preview · Article · Apr 2015 · The Journal of molecular diagnostics: JMD
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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.
    No preview · Article · Mar 2015 · Journal of Medical Genetics
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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.
    Full-text · Article · Mar 2015 · Scientific Reports
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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.
    Full-text · Article · Mar 2015 · American Journal of Translational Research
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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.
    Preview · Article · Feb 2015 · Frontiers in Genetics

Publication Stats

3k Citations
663.75 Total Impact Points

Institutions

  • 2015
    • Fundação Oswaldo Cruz
      Rio de Janeiro, Rio de Janeiro, Brazil
  • 2012-2015
    • Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
      • Instituto da Criança (ICr)
      San Paulo, São Paulo, Brazil
  • 2007-2015
    • Texas Heart Institute
      Houston, Texas, United States
    • Universidade Federal do Espírito Santo
      • Departamento de Ciências Fisiológicas
      Victoria, Espírito Santo, Brazil
  • 1998-2015
    • University of São Paulo
      • Faculty of Medicine (FM)
      San Paulo, São Paulo, Brazil
  • 2002-2012
    • Instituto do Coração
      San Paulo, São Paulo, Brazil
  • 2011
    • Universidade Federal de São Paulo
      San Paulo, São Paulo, Brazil
  • 2004
    • Brigham and Women's Hospital
      • Department of Medicine
      Boston, Massachusetts, United States