Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 66
Filtrar
Mais filtros










Intervalo de ano de publicação
1.
Am J Hum Biol ; 31(5): e23278, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31237064

RESUMO

OBJECTIVES: This article aims to assess the contribution of genomic ancestry and socioeconomic status to obesity in a sample of admixed Latin Americans. METHODS: The study comprised 6776 adult volunteers from Brazil, Chile, Colombia, Mexico, and Peru. Each volunteer completed a questionnaire about socioeconomic variables. Anthropometric variables such as weight, height, waist, and hip circumference were measured to calculate body indices: body mass index, waist-to-hip ratio and waist-to-height ratio (WHtR). Genetic data were extracted from blood samples, and ancestry was estimated using chip genotypes. Multiple linear regression was used to evaluate the relationship between the indices and ancestry, educational level, and economic well-being. The body indices were dichotomized to obesity indices by using appropriate thresholds. Odds ratios were calculated for each obesity index. RESULTS: The sample showed high percentages of obesity by all measurements. However, indices did not overlap consistently when classifying obesity. WHtR resulted in the highest prevalence of obesity. Overall, women with low education level and men with high economic wellness were more likely to be obese. American ancestry was statistically associated with obesity indices, although to a lesser extent than socioeconomic variables. CONCLUSIONS: The proportion of obesity was heavily dependent on the index and the population. Genomic ancestry has a significant influence on the anthropometric measurements, especially on central adiposity. As a whole, we detected a large interpopulation variation that suggests that better approaches to overweight and obesity phenotypes are needed in order to obtain more precise reference values.

2.
BMJ Open ; 9(4): e025530, 2019 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-31005922

RESUMO

INTRODUCTION: Pain constitutes a major component of the global burden of diseases. Recent studies suggest a strong genetic contribution to pain susceptibility and severity. Whereas most of the available evidence relies on candidate gene association or linkage studies, research on the genetic basis of pain sensitivity using genome-wide association studies (GWAS) is still in its infancy. This protocol describes a proposed GWAS on genetic contributions to baseline pain sensitivity and nociceptive sensitisation in a sample of unrelated healthy individuals of mixed Latin American ancestry. METHODS AND ANALYSIS: A GWAS on genetic contributions to pain sensitivity in the naïve state and following nociceptive sensitisation will be conducted in unrelated healthy individuals of mixed ancestry. Mechanical and thermal pain sensitivity will be evaluated with a battery of quantitative sensory tests evaluating pain thresholds. In addition, variation in mechanical and thermal sensitisation following topical application of mustard oil to the skin will be evaluated. ETHICS AND DISSEMINATION: This study received ethical approval from the University College London research ethics committee (3352/001) and from the bioethics committee of the Odontology Faculty at the University of Antioquia (CONCEPTO 01-2013). Findings will be disseminated to commissioners, clinicians and service users via papers and presentations at international conferences.

3.
World J Biol Psychiatry ; 20(5): 340-351, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30907211

RESUMO

Recently, there has been a major shift in the field of psychiatry towards the exploration of complex relationships between blood-based biomarkers and the pathophysiology of psychiatric and neuropsychiatric disorders. However, issues with study reproducibility, validity and reliability have hindered progress towards the identification of clinically relevant biomarkers for psychiatry. The achievement of laboratory validity is a crucial first step for the posterior development of clinical validity. There is evidence that the variability observed in blood-based research studies may be minimised with the implementation of standardised pre-analytical methods and uniform clinical protocols (i.e., pre-venipuncture). It has been documented that errors made in the pre-analytical phase account for 46-68.2% of laboratory testing errors. Thus, standardising clinical assessment, ethical procedures and pre-analytical phase of clinical research is essential for the reproducibility, validity and reliability of blood marker assessment, and reducing the risk of invalid test results. Various other areas of research have already moved towards guidelines for the standardised collection of blood-based biomarkers. Here we aim to provide a set of guidelines that we believe would improve biomarker research: (1) pre-venipuncture information and documentation, (2) ethics of participant consent and (3) pre-analytical methods. Ultimately, we hope this will assist study planning and will improve data comparison across studies allowing for the discovery of biomarkers in psychiatry with both laboratorial and clinical validity.

4.
Int. braz. j. urol ; 45(1): 161-168, Jan.-Feb. 2019. tab, graf
Artigo em Inglês | LILACS-Express | ID: biblio-989967

RESUMO

ABSTRACT High-fat diet-induced obesity is associated with metabolic disorders. The Brazil nut has bioactive substances and has been used to control the damage caused by obesity in several organs. The work intended to show the damage caused by high-fat diet in the bladder wall and if the Brazil nut oil added to the diet could ameliorate or reverse this effect. Sixty-day-old rats were divided into two groups: C (control, n = 30) and HF (high-fat, n = 30) diets. At 90 days, 10 animals of each group were sacrificed. The others were divided into 4 groups: C and HF (animals that maintained their previous diet, n = 10 for each group) and C / Bno and HF / Bno (animals whose control or high-fat diet was supplemented by Brazil nut oil, n = 10 for each group). Sacrifice occurred at 120 days, and the bladders were removed and analyzed. Epithelial height was increased in the HF compared to the C group. In contrast, the C / Bno had a lower epithelial height compared to the others. The percentage of collagen between the detrusor muscle fibers was significantly greater in C / Bno, HF and HF / Bno than in control group. The HF had a larger muscle fiber diameter than the C group, while the C / Bno presented lower values than the HF and HF / Bno groups. HF diets induced bladder wall damage. These changes in the rat's bladder wall were partially reversed by the Bno.

5.
Nat Commun ; 10(1): 358, 2019 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-30664655

RESUMO

We report a genome-wide association scan in >6,000 Latin Americans for pigmentation of skin and eyes. We found eighteen signals of association at twelve genomic regions. These include one novel locus for skin pigmentation (in 10q26) and three novel loci for eye pigmentation (in 1q32, 20q13 and 22q12). We demonstrate the presence of multiple independent signals of association in the 11q14 and 15q13 regions (comprising the GRM5/TYR and HERC2/OCA2 genes, respectively) and several epistatic interactions among independently associated alleles. Strongest association with skin pigmentation at 19p13 was observed for an Y182H missense variant (common only in East Asians and Native Americans) in MFSD12, a gene recently associated with skin pigmentation in Africans. We show that the frequency of the derived allele at Y182H is significantly correlated with lower solar radiation intensity in East Asia and infer that MFSD12 was under selection in East Asians, probably after their split from Europeans.


Assuntos
Epistasia Genética , Cor de Olho/genética , Genoma Humano , Locos de Características Quantitativas , Pigmentação da Pele/genética , Alelos , Grupo com Ancestrais do Continente Asiático , Evolução Biológica , Grupos Étnicos , Grupo com Ancestrais do Continente Europeu , Feminino , Expressão Gênica , Frequência do Gene , Genética Populacional , Estudo de Associação Genômica Ampla , Fatores de Troca do Nucleotídeo Guanina/genética , Humanos , América Latina , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana Transportadoras/genética , Polimorfismo de Nucleotídeo Único , Receptor de Glutamato Metabotrópico 5/genética
6.
Int Braz J Urol ; 45(1): 161-168, 2019 Jan-Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30556993

RESUMO

High-fat diet-induced obesity is associated with metabolic disorders. The Brazil nut has bioactive substances and has been used to control the damage caused by obesity in several organs. The work intended to show the damage caused by high-fat diet in the bladder wall and if the Brazil nut oil added to the diet could ameliorate or reverse this effect. Sixty-day-old rats were divided into two groups: C (control, n = 30) and HF (high-fat, n = 30) diets. At 90 days, 10 animals of each group were sacrificed. The others were divided into 4 groups: C and HF (animals that maintained their previous diet, n = 10 for each group) and C / Bno and HF / Bno (animals whose control or high-fat diet was supplemented by Brazil nut oil, n = 10 for each group). Sacrifice occurred at 120 days, and the bladders were removed and analyzed. Epithelial height was increased in the HF compared to the C group. In contrast, the C / Bno had a lower epithelial height compared to the others. The percentage of collagen between the detrusor muscle fibers was significantly greater in C / Bno, HF and HF / Bno than in control group. The HF had a larger muscle fiber diameter than the C group, while the C / Bno presented lower values than the HF and HF / Bno groups. HF diets induced bladder wall damage. These changes in the rat's bladder wall were partially reversed by the Bno.


Assuntos
Bertholletia/química , Dieta Hiperlipídica , Suplementos Nutricionais , Óleos Vegetais/farmacologia , Bexiga Urinária/efeitos dos fármacos , Animais , Masculino , Ratos , Fatores de Tempo
7.
Am J Phys Anthropol ; 168(3): 438-447, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30582632

RESUMO

OBJECTIVES: To investigate the variation in dental nonmetric traits and to evaluate the utility of this variation for inferring genetic ancestry proportions in a sample of admixed Latin Americans. MATERIALS AND METHODS: We characterized a sample from Colombia (N = 477) for 34 dental traits and obtained estimates of individual Native American, European, and African ancestry using genome-wide SNP data. We tested for correlation between dental traits, genetic ancestry, age, and sex. We carried out a biodistance analysis between the Colombian sample and reference continental population samples using the mean measure of divergence statistic calculated from dental trait frequencies. We evaluated the inference of genetic ancestry from dental traits using a regression approach (with 10-fold cross-validation) as well as by testing the correlation between estimates of ancestry obtained from genetic and dental data. RESULTS: Latin Americans show intermediate dental trait frequencies when compared to Native Americans, Europeans, and Africans. Significant correlations were observed for several dental traits, genetic ancestry, age, and sex. The biodistance analysis displayed a closer relationship of Colombians to Europeans than to Native Americans and Africans. Mean ancestry estimates obtained from the dental data are similar to the genetic estimates (Native American: 32% vs. 28%, European: 59% vs. 63%, and African: 9% vs. 9%, respectively). However, dental features provided low predictive power for genetic ancestry of individuals in both approaches tested (R2 < 5% for all genetic ancestries across methods). DISCUSSION: The frequency of dental traits in Latin Americans reflects their admixed Native American, European and African ancestry and can provide reasonable average estimates of genetic ancestry. However, the accuracy of individual genetic ancestry estimates is relatively low, probably influenced by the continental differentiation of dental traits, their genetic architecture, and the distribution of genetic ancestry in the individuals examined.

8.
Nat Commun ; 9(1): 5388, 2018 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-30568240

RESUMO

Historical records and genetic analyses indicate that Latin Americans trace their ancestry mainly to the intermixing (admixture) of Native Americans, Europeans and Sub-Saharan Africans. Using novel haplotype-based methods, here we infer sub-continental ancestry in over 6,500 Latin Americans and evaluate the impact of regional ancestry variation on physical appearance. We find that Native American ancestry components in Latin Americans correspond geographically to the present-day genetic structure of Native groups, and that sources of non-Native ancestry, and admixture timings, match documented migratory flows. We also detect South/East Mediterranean ancestry across Latin America, probably stemming mostly from the clandestine colonial migration of Christian converts of non-European origin (Conversos). Furthermore, we find that ancestry related to highland (Central Andean) versus lowland (Mapuche) Natives is associated with variation in facial features, particularly nose morphology, and detect significant differences in allele frequencies between these groups at loci previously associated with nose morphology in this sample.


Assuntos
Migração Humana , Índios Norte-Americanos/genética , Índios Sul-Americanos/genética , Haplótipos , Humanos , México , Nariz/anatomia & histologia , América do Sul
9.
Int J Cardiol ; 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30305239

RESUMO

BACKGROUND: Serum uric acid (SUA) is a heritable trait associated with cardiovascular risk factors and coronary artery disease (CAD). Genome wide association studies (GWAS) have identified several genes associated with SUA, mainly in European populations. However, to date there are few GWAS in Latino populations, and the role of SUA-associated single nucleotide polymorphisms (SNPs) in cardiovascular disease has not been studied in the Mexican population. METHODS: We performed genome-wide SUA association study in 2153 Mexican children and adults, evaluated whether genetic effects were modified by sex and obesity, and used a Mendelian randomization approach in an independent cohort to study the role of SUA modifying genetic variants in premature CAD. RESULTS: Only two loci were associated with SUA levels: SLC2A9 (ß = -0.47 mg/dl, P = 1.57 × 10-42 for lead SNP rs7678287) and ABCG2 (ß = 0.23 mg/dl, P = 2.42 × 10-10 for lead SNP rs2231142). No significant interaction between SLC2A9 rs7678287 and ABCG2 rs2231142 genotypes and obesity was observed. However, a significant ABCG2 rs2231142 genotype*sex interaction (P = 0.001) was observed in adults but not in children. Although SUA levels were associated with premature CAD, metabolic syndrome and decreased glomerular filtration rate (eGFR), only ABCG2 rs2231142 was associated with decreased eGFR in the premature CAD group. CONCLUSIONS: SUA elevation was independently associated with premature CAD, metabolic syndrome and decreased eGFR in the Mexican population. However, a Mendelian randomization approach using the lead SUA-associated SNPs (SLC2A9 and ABCG2) did not support a causal role of elevated SUA levels for premature CAD.

10.
PLoS Genet ; 14(9): e1007640, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30248107

RESUMO

Hair plays an important role in primates and is clearly subject to adaptive selection. While humans have lost most facial hair, eyebrows are a notable exception. Eyebrow thickness is heritable and widely believed to be subject to sexual selection. Nevertheless, few genomic studies have explored its genetic basis. Here, we performed a genome-wide scan for eyebrow thickness in 2961 Han Chinese. We identified two new loci of genome-wide significance, at 3q26.33 near SOX2 (rs1345417: P = 6.51×10-10) and at 5q13.2 near FOXD1 (rs12651896: P = 1.73×10-8). We further replicated our findings in the Uyghurs, a population from China characterized by East Asian-European admixture (N = 721), the CANDELA cohort from five Latin American countries (N = 2301), and the Rotterdam Study cohort of Dutch Europeans (N = 4411). A meta-analysis combining the full GWAS results from the three cohorts of full or partial Asian descent (Han Chinese, Uyghur and Latin Americans, N = 5983) highlighted a third signal of genome-wide significance at 2q12.3 (rs1866188: P = 5.81×10-11) near EDAR. We performed fine-mapping and prioritized four variants for further experimental verification. CRISPR/Cas9-mediated gene editing provided evidence that rs1345417 and rs12651896 affect the transcriptional activity of the nearby SOX2 and FOXD1 genes, which are both involved in hair development. Finally, suitable statistical analyses revealed that none of the associated variants showed clear signals of selection in any of the populations tested. Contrary to popular speculation, we found no evidence that eyebrow thickness is subject to strong selective pressure.

11.
Biomed Res Int ; 2018: 6030646, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29850540

RESUMO

Vitamin D deficiency is common in pregnant women and infants. The present study aimed to investigate the effects of vitamin D restricted diet on the Wistar rats offspring penis morphology. Mother rats received either standard diet (SC) or vitamin D restricted (VitD) diet. At birth, offspring were divided into SC/SC (from SC mothers, fed with SC diet) and VitD/VitD (from VitD mothers, fed with VitD diet). After euthanasia the penises were processed for histomorphometric analysis. The VitD/VitD offspring displayed metabolic changes and reduction in the cross-sectional area of the penis, corpus cavernosum, tunica albuginea, and increased area of the corpus spongiosum. The connective tissue, smooth muscle, and cell proliferation percentages were greater in the corpus cavernosum and corpus spongiosum in the VitD/VitD offspring. The percentages of sinusoidal spaces and elastic fibers in the corpus cavernosum decreased. The elastic fibers in the tunica albuginea of the corpus spongiosum in the VitD/VitD offspring were reduced. Vitamin D restriction during perinatal and postnatal periods induced metabolic and structural changes and represented important risk factors for erectile dysfunction in the penis of the adult offspring. These findings suggest that vitamin D is an important micronutrient in maintaining the cytoarchitecture of the penis.


Assuntos
Pênis , Complicações na Gravidez , Deficiência de Vitamina D , Vitamina D , Animais , Feminino , Masculino , Pênis/citologia , Pênis/efeitos dos fármacos , Pênis/crescimento & desenvolvimento , Gravidez , Ratos , Ratos Wistar , Vitamina D/administração & dosagem , Vitamina D/sangue , Vitamina D/farmacologia
12.
Sci Rep ; 8(1): 963, 2018 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-29343858

RESUMO

Facial asymmetries are usually measured and interpreted as proxies to developmental noise. However, analyses focused on its developmental and genetic architecture are scarce. To advance on this topic, studies based on a comprehensive and simultaneous analysis of modularity, morphological integration and facial asymmetries including both phenotypic and genomic information are needed. Here we explore several modularity hypotheses on a sample of Latin American mestizos, in order to test if modularity and integration patterns differ across several genomic ancestry backgrounds. To do so, 4104 individuals were analyzed using 3D photogrammetry reconstructions and a set of 34 facial landmarks placed on each individual. We found a pattern of modularity and integration that is conserved across sub-samples differing in their genomic ancestry background. Specifically, a signal of modularity based on functional demands and organization of the face is regularly observed across the whole sample. Our results shed more light on previous evidence obtained from Genome Wide Association Studies performed on the same samples, indicating the action of different genomic regions contributing to the expression of the nose and mouth facial phenotypes. Our results also indicate that large samples including phenotypic and genomic metadata enable a better understanding of the developmental and genetic architecture of craniofacial phenotypes.


Assuntos
Face/anatomia & histologia , Face/fisiologia , Desenvolvimento Maxilofacial/genética , Adolescente , Adulto , Feminino , Estudo de Associação Genômica Ampla/métodos , Humanos , América Latina , Masculino , Pessoa de Meia-Idade , Fenótipo , Adulto Jovem
13.
Prostate ; 78(4): 289-293, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29315701

RESUMO

BACKGROUND: McNeal divided the human prostate into three major anatomical areas: the peripheral zone (PZ), the central zone (CZ), and the transition zone (TZ). Each of these areas is biologically and histologically distinct. The PZ and TZ have clinical significance and are associated with prostate cancer (PC) and benign prostatic hyperplasia (BPH), respectively. Therefore, the objective of the present study was to quantitatively and qualitatively analyze the parenchymal and stromal components that constitute the different prostate zones. METHODS: We assessed 19 samples from each prostate zone. The samples were obtained from necropsies of young people between 18 and 32 years of age with intact urogenital tracts. The samples were fixed in 4% buffered formalin and processed for paraffin embedding. Sections with a thickness of five micrometres were obtained from each sample. The sections were stained using histochemical and immunohistochemical techniques to identify the acinar and stromal components of each zone. Photomicrographs were obtained for morphometric analysis using an algorithm based on color segmentation. Data were analyzed using one-way analysis of variance (ANOVA) with the Bonferroni post-test. Differences with P < 0.05 were regarded as statistically significant. RESULTS: Collagen fibres were more numerous in the TZ (+40.26%; P = 0.0230) than in the PZ. Muscle fibres were also more numerous in the TZ (+47.05%; P = 0.0120) than in the PZ. Elastic system fibres in the TZ significantly differed from those in the PZ (+84.61%; P = 0.0012) and the CZ (+61.66%; P = 0.0074). Similarly, nerves in the PZ (-42.86%; P = 0.0107) significantly differed from nerves in the CZ. Epithelial height was lower in the TZ than in the PZ (-30.17%; P = 0.0034) and the CZ (-25.01%; P = 0.0330). CONCLUSION: Our objective, quantitative data regarding the various elements that constitute the normal prostate stroma allowed us to reveal differences among prostate zones. This study established patterns for normal parameters and may be used for posterior comparisons in histopathological analysis.

14.
Hum Mol Genet ; 27(3): 559-575, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29220522

RESUMO

Shape variation of human head hair shows striking variation within and between human populations, while its genetic basis is far from being understood. We performed a series of genome-wide association studies (GWASs) and replication studies in a total of 28 964 subjects from 9 cohorts from multiple geographic origins. A meta-analysis of three European GWASs identified 8 novel loci (1p36.23 ERRFI1/SLC45A1, 1p36.22 PEX14, 1p36.13 PADI3, 2p13.3 TGFA, 11p14.1 LGR4, 12q13.13 HOXC13, 17q21.2 KRTAP, and 20q13.33 PTK6), and confirmed 4 previously known ones (1q21.3 TCHH/TCHHL1/LCE3E, 2q35 WNT10A, 4q21.21 FRAS1, and 10p14 LINC00708/GATA3), all showing genome-wide significant association with hair shape (P < 5e-8). All except one (1p36.22 PEX14) were replicated with nominal significance in at least one of the 6 additional cohorts of European, Native American and East Asian origins. Three additional previously known genes (EDAR, OFCC1, and PRSS53) were confirmed at the nominal significance level. A multivariable regression model revealed that 14 SNPs from different genes significantly and independently contribute to hair shape variation, reaching a cross-validated AUC value of 0.66 (95% CI: 0.62-0.70) and an AUC value of 0.64 in an independent validation cohort, providing an improved accuracy compared with a previous model. Prediction outcomes of 2504 individuals from a multiethnic sample were largely consistent with general knowledge on the global distribution of hair shape variation. Our study thus delivers target genes and DNA variants for future functional studies to further evaluate the molecular basis of hair shape in humans.

15.
World J Biol Psychiatry ; 19(4): 244-328, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29076399

RESUMO

In the 12 years since the publication of the first Consensus Paper of the WFSBP on biomarkers of neurodegenerative dementias, enormous advancement has taken place in the field, and the Task Force takes now the opportunity to extend and update the original paper. New concepts of Alzheimer's disease (AD) and the conceptual interactions between AD and dementia due to AD were developed, resulting in two sets for diagnostic/research criteria. Procedures for pre-analytical sample handling, biobanking, analyses and post-analytical interpretation of the results were intensively studied and optimised. A global quality control project was introduced to evaluate and monitor the inter-centre variability in measurements with the goal of harmonisation of results. Contexts of use and how to approach candidate biomarkers in biological specimens other than cerebrospinal fluid (CSF), e.g. blood, were precisely defined. Important development was achieved in neuroimaging techniques, including studies comparing amyloid-ß positron emission tomography results to fluid-based modalities. Similarly, development in research laboratory technologies, such as ultra-sensitive methods, raises our hopes to further improve analytical and diagnostic accuracy of classic and novel candidate biomarkers. Synergistically, advancement in clinical trials of anti-dementia therapies energises and motivates the efforts to find and optimise the most reliable early diagnostic modalities. Finally, the first studies were published addressing the potential of cost-effectiveness of the biomarkers-based diagnosis of neurodegenerative disorders.


Assuntos
Psiquiatria Biológica/normas , Biomarcadores , Consenso , Demência/diagnóstico , Doenças Neurodegenerativas/diagnóstico , Sociedades Médicas/normas , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Demência/sangue , Demência/líquido cefalorraquidiano , Humanos , Doenças Neurodegenerativas/sangue , Doenças Neurodegenerativas/líquido cefalorraquidiano
16.
Am J Hum Genet ; 101(6): 913-924, 2017 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-29198719

RESUMO

The genetic basis of earlobe attachment has been a matter of debate since the early 20th century, such that geneticists argue both for and against polygenic inheritance. Recent genetic studies have identified a few loci associated with the trait, but large-scale analyses are still lacking. Here, we performed a genome-wide association study of lobe attachment in a multiethnic sample of 74,660 individuals from four cohorts (three with the trait scored by an expert rater and one with the trait self-reported). Meta-analysis of the three expert-rater-scored cohorts revealed six associated loci harboring numerous candidate genes, including EDAR, SP5, MRPS22, ADGRG6 (GPR126), KIAA1217, and PAX9. The large self-reported 23andMe cohort recapitulated each of these six loci. Moreover, meta-analysis across all four cohorts revealed a total of 49 significant (p < 5 × 10-8) loci. Annotation and enrichment analyses of these 49 loci showed strong evidence of genes involved in ear development and syndromes with auricular phenotypes. RNA sequencing data from both human fetal ear and mouse second branchial arch tissue confirmed that genes located among associated loci showed evidence of expression. These results provide strong evidence for the polygenic nature of earlobe attachment and offer insights into the biological basis of normal and abnormal ear development.


Assuntos
Orelha/anatomia & histologia , Herança Multifatorial/genética , Locos de Características Quantitativas/genética , Adolescente , Adulto , Animais , Região Branquial/anatomia & histologia , Criança , Pré-Escolar , Proteínas de Ligação a DNA/genética , Receptor Edar/genética , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Camundongos , Pessoa de Meia-Idade , Proteínas Mitocondriais/genética , Fator de Transcrição PAX9/genética , Proteínas/genética , Receptores Acoplados a Proteínas-G/genética , Proteínas Ribossômicas/genética , Fatores de Transcrição/genética , Adulto Jovem
17.
Int. braz. j. urol ; 43(5): 957-965, Sept.-Oct. 2017. tab, graf
Artigo em Inglês | LILACS-Express | ID: biblio-892904

RESUMO

ABSTRACT Purpose: To evaluate if late hormonal replacement is able to recover the prostatic tissue modified by androgenic deprivation. Materials and Methods: 24 rats were assigned into a Sham group; an androgen deficient group, submitted to bilateral orchiectomy (Orch); and a group submitted to bilateral orchiectomy followed by testosterone replacement therapy (Orch+T). After 60 days from surgery blood was collected for determination of testosterone levels and the ventral prostate was collected for quantitative and qualitative microscopic analysis. The acinar epithelium height, the number of mast cells per field, and the densities of collagen fibers and acinar lumen were analyzed by stereological methods under light microscopy. The muscle fibers and types of collagen fibers were qualitatively assessed by scanning electron microscopy and polarization microscopy. Results: Hormone depletion (in group Orch) and return to normal levels (in group Orch+T) were effective as verified by serum testosterone analysis. The androgen deprivation promoted several alterations in the prostate: the acinar epithelium height diminished from 16.58±0.47 to 11.48±0.29μm; the number of mast cells per field presented increased from 0.45±0.07 to 2.83±0.25; collagen fibers density increased from 5.83±0.92 to 24.70±1.56%; and acinar lumen density decreased from 36.78±2.14 to 16.47±1.31%. Smooth muscle was also increased in Orch animals, and type I collagen fibers became more predominant in these animals. With the exception of the densities of collagen fibers and acinar lumen, in animals receiving testosterone replacement therapy all parameters became statistically similar to Sham. Collagen fibers density became lower and acinar lumen density became higher in Orch+T animals, when compared to Sham. This is the first study to demonstrate a relation between mast cells and testosterone levels in the prostate. This cells have been implicated in prostatic cancer and benign hyperplasia, although its specific role is not understood. Conclusion: Testosterone deprivation promotes major changes in the prostate of rats. The hormonal replacement therapy was effective in reversing these alterations.

18.
PLoS Genet ; 13(5): e1006756, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28542165

RESUMO

Latin Americans are highly heterogeneous regarding the type of Native American ancestry. Consideration of specific associations with common diseases may lead to substantial advances in unraveling of disease etiology and disease prevention. Here we investigate possible associations between the type of Native American ancestry and leading causes of death. After an aggregate-data study based on genome-wide genotype data from 1805 admixed Chileans and 639,789 deaths, we validate an identified association with gallbladder cancer relying on individual data from 64 gallbladder cancer patients, with and without a family history, and 170 healthy controls. Native American proportions were markedly underestimated when the two main types of Native American ancestry in Chile, originated from the Mapuche and Aymara indigenous peoples, were combined together. Consideration of the type of Native American ancestry was crucial to identify disease associations. Native American ancestry showed no association with gallbladder cancer mortality (P = 0.26). By contrast, each 1% increase in the Mapuche proportion represented a 3.7% increased mortality risk by gallbladder cancer (95%CI 3.1-4.3%, P = 6×10-27). Individual-data results and extensive sensitivity analyses confirmed the association between Mapuche ancestry and gallbladder cancer. Increasing Mapuche proportions were also associated with an increased mortality due to asthma and, interestingly, with a decreased mortality by diabetes. The mortality due to skin, bladder, larynx, bronchus and lung cancers increased with increasing Aymara proportions. Described methods should be considered in future studies on human population genetics and human health. Complementary individual-based studies are needed to apportion the genetic and non-genetic components of associations identified relying on aggregate-data.


Assuntos
Neoplasias da Vesícula Biliar/genética , Estudo de Associação Genômica Ampla , Índios Norte-Americanos/genética , Adolescente , Adulto , Chile , Feminino , Neoplasias da Vesícula Biliar/mortalidade , Genética Populacional , Genoma Humano , Genótipo , Humanos , América Latina/epidemiologia , Masculino , Fatores de Risco
19.
Int Braz J Urol ; 43(5): 957-965, 2017 Sep-Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28379662

RESUMO

PURPOSE: To evaluate if late hormonal replacement is able to recover the prostatic tissue modified by androgenic deprivation. MATERIALS AND METHODS: 24 rats were assigned into a Sham group; an androgen deficient group, submitted to bilateral orchiectomy (Orch); and a group submitted to bilateral orchiectomy followed by testosterone replacement therapy (Orch+T). After 60 days from surgery blood was collected for determination of testosterone levels and the ventral prostate was collected for quantitative and qualitative microscopic analysis. The acinar epithelium height, the number of mast cells per field, and the densities of collagen fibers and acinar lumen were analyzed by stereological methods under light microscopy. The muscle fibers and types of collagen fibers were qualitatively assessed by scanning electron microscopy and polarization microscopy. RESULTS: Hormone depletion (in group Orch) and return to normal levels (in group Orch+T) were effective as verified by serum testosterone analysis. The androgen deprivation promoted several alterations in the prostate: the acinar epithelium height diminished from 16.58±0.47 to 11.48±0.29µm; the number of mast cells per field presented increased from 0.45±0.07 to 2.83±0.25; collagen fibers density increased from 5.83±0.92 to 24.70±1.56%; and acinar lumen density decreased from 36.78±2.14 to 16.47±1.31%. Smooth muscle was also increased in Orch animals, and type I collagen fibers became more predominant in these animals. With the exception of the densities of collagen fibers and acinar lumen, in animals receiving testosterone replacement therapy all parameters became statistically similar to Sham. Collagen fibers density became lower and acinar lumen density became higher in Orch+T animals, when compared to Sham. This is the first study to demonstrate a relation between mast cells and testosterone levels in the prostate. This cells have been implicated in prostatic cancer and benign hyperplasia, although its specific role is not understood. CONCLUSION: Testosterone deprivation promotes major changes in the prostate of rats. The hormonal replacement therapy was effective in reversing these alterations.


Assuntos
Androgênios/deficiência , Terapia de Reposição Hormonal , Orquiectomia , Próstata/patologia , Próstata/ultraestrutura , Testosterona/sangue , Animais , Masculino , Próstata/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA