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BACKGROUND: Calcific aortic valve disease is characterized by an abnormal mineralization of the aortic valve. Osteogenic activity in the aortic valve is under the control of NOTCH1, which regulates the expression of key pro-osteogenic genes such as RUNX2 and BMP2. Long noncoding RNAs (lncRNAs) may reprogram cells by altering the gene expression pattern. METHODS: Multidimensional genomic profiling was performed in human aortic valves to document the expression of lncRNAs and the DNA methylation pattern in calcific aortic valve disease. In-depth functional assays were carried out to document the impact of lncRNA on the mineralization of the aortic valve. RESULTS: We documented that lncRNA H19 (H19) was increased in calcific aortic valve disease. Hypomethylation of the promoter region was observed in mineralized aortic valves and was inversely associated with H19 expression. Knockdown and overexpression experiments showed that H19 induces a strong osteogenic phenotype by altering the NOTCH1 pathway. Gene promoter analyses showed that H19 silenced NOTCH1 by preventing the recruitment of p53 to its promoter. A knockdown of H19 in valve interstitial cells (VICs) increased the expression of NOTCH1 and decreased the level of RUNX2 and BMP2, 2 downstream targets repressed by NOTCH1. In rescue experiments, the transfection of a vector encoding for the active Notch intracellular domain prevented H19-induced mineralization of valve interstitial cells. CONCLUSIONS: These findings indicate that a dysregulation of DNA methylation in the promoter of H19 during calcific aortic valve disease is associated with a higher expression of this lncRNA, which promotes an osteogenic program by interfering with the expression of NOTCH1.
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Estenosis de la Válvula Aórtica/genética , Válvula Aórtica/patología , Calcinosis/genética , Metilación de ADN , ARN Largo no Codificante/metabolismo , Receptor Notch1/genética , Receptor Notch1/metabolismo , Anciano , Válvula Aórtica/citología , Válvula Aórtica/metabolismo , Estenosis de la Válvula Aórtica/patología , Proteína Morfogenética Ósea 2/análisis , Calcinosis/patología , Células Cultivadas , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Femenino , Genes Reporteros , Células HEK293 , Humanos , Masculino , Persona de Mediana Edad , Regiones Promotoras Genéticas , Interferencia de ARN , ARN Largo no Codificante/antagonistas & inhibidores , ARN Largo no Codificante/genética , ARN Interferente Pequeño/metabolismo , Receptor Notch1/antagonistas & inhibidores , Proteína p53 Supresora de Tumor/análisisRESUMEN
The molecular mechanisms leading to premature development of aortic valve stenosis (AS) in individuals with a bicuspid aortic valve are unknown. The objective of this study was to identify genes differentially expressed between calcified bicuspid aortic valves (BAVc) and tricuspid valves with (TAVc) and without (TAVn) AS using RNA sequencing (RNA-Seq). We collected 10 human BAVc and nine TAVc from men who underwent primary aortic valve replacement. Eight TAVn were obtained from men who underwent heart transplantation. mRNA levels were measured by RNA-Seq and compared between valve groups. Two genes were upregulated, and none were downregulated in BAVc compared with TAVc, suggesting a similar gene expression response to AS in individuals with bicuspid and tricuspid valves. There were 462 genes upregulated and 282 downregulated in BAVc compared with TAVn. In TAVc compared with TAVn, 329 genes were up- and 170 were downregulated. A total of 273 upregulated and 147 downregulated genes were concordantly altered between BAVc vs. TAVn and TAVc vs. TAVn, which represent 56 and 84% of significant genes in the first and second comparisons, respectively. This indicates that extra genes and pathways were altered in BAVc. Shared pathways between calcified (BAVc and TAVc) and normal (TAVn) aortic valves were also more extensively altered in BAVc. The top pathway enriched for genes differentially expressed in calcified compared with normal valves was fibrosis, which support the remodeling process as a therapeutic target. These findings are relevant to understand the molecular basis of AS in patients with bicuspid and tricuspid valves.
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Válvula Aórtica/anomalías , Enfermedades de las Válvulas Cardíacas/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Transcriptoma/genética , Válvula Tricúspide/metabolismo , Válvula Aórtica/metabolismo , Válvula Aórtica/patología , Estenosis de la Válvula Aórtica , Enfermedad de la Válvula Aórtica Bicúspide , Calcinosis , Regulación hacia Abajo/genética , Humanos , Masculino , Análisis de Secuencia de ARN/métodos , Regulación hacia Arriba/genéticaRESUMEN
OBJECTIVE: Studies have shown that high-density lipoprotein (HDL)-raising compounds induce regression of aortic valve stenosis (AVS) in animal models. However, whether patients with AVS have an impaired HDL metabolism is unknown. APPROACH AND RESULTS: A total of 1435 single nucleotide polymorphisms in genes associated with HDL cholesterol levels (in or around GALNT2, LPL, ABCA1, APOA5, SCARB1, LIPC, CETP, LCAT, LIPG, APOC4, and PLTP) were genotyped in 382 patients with echocardiography-confirmed AVS (aortic jet velocity ≥2.5 m/s) and 401 controls. After control for multiple testing, none of the genetic variants showed a positive association with case/control status (adjusted P≥0.05 for all single nucleotide polymorphisms tested). In a subsample of this cohort, HDL cholesterol levels, apolipoprotein AI levels, lecithin-cholesterol acyltransferase activity, pre-ß-HDL, HDL size, and 4 parameters of cholesterol efflux capacity were measured in apolipoprotein B-depleted serum samples from 86 patients with and 86 patients without AVS. Cholesterol efflux capacity was measured using J774 macrophages with and without stimulation of ATP-binding cassette A-1 expression by cAMP, and HepG2 hepatocytes for scavenger receptor class B type 1-mediated efflux. None of these parameters were different between cases and controls. However, compared with patients without coronary artery disease, sera from patients with coronary artery disease had lower HDL cholesterol levels, scavenger receptor class B type 1-mediated efflux, and HDL size (P≤0.003), independently of the presence or absence of AVS. CONCLUSIONS: Results of the present study suggest that, based on HDL genetics and HDL functionality, HDL metabolism does not seem to predict the risk of AVS. Because of our limited sample size, additional studies are needed to confirm these findings.
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Estenosis de la Válvula Aórtica/genética , Lipoproteínas HDL/genética , Polimorfismo de Nucleótido Simple , Anciano , Animales , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/fisiopatología , Estenosis de la Válvula Aórtica/sangre , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/fisiopatología , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , HDL-Colesterol/sangre , HDL-Colesterol/genética , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/genética , Femenino , Marcadores Genéticos , Predisposición Genética a la Enfermedad , Células Hep G2 , Hepatocitos/metabolismo , Humanos , Lipoproteínas HDL/sangre , Modelos Logísticos , Macrófagos/metabolismo , Masculino , Ratones , Persona de Mediana Edad , Paris , Fenotipo , Estudios Prospectivos , Quebec , Factores de Riesgo , UltrasonografíaRESUMEN
BACKGROUND AND AIM OF THE STUDY: Calcific aortic valve stenosis (AS) affects 2-5% of the population aged > 65 years. Functional DNA variants at the NOTCH1 locus result in bicuspid aortic valve (BAV) and severe valve calcification. The contribution of these variants to AS in the population with tricuspid aortic valve (TAV) remains to be determined. METHODS: Fourteen genetic variants surrounding the NOTCH1 gene were genotyped, including rare mutations previously reported, and common polymorphisms. The study involved 457 French Canadian patients with severe tricuspid AS. Genotyping was carried out using the Illumina BeadXpress platform. Allele frequencies of common single nucleotide polymorphisms (SNPs) for patients with AS were compared to a shared control group of European ancestry (n = 3,294). In total, 88 ancestry-informative markers were used to correct for population stratification. RESULTS: The mutation R1107X, previously associated with AS and BAV, was identified in a relatively young patient (aged 58 years). The mutations R1279H and V2285I were detected in 18 and 14 heterozygotes, respectively. A common polymorphism (rs13290979) located in intron 2 was significantly associated with AS (p = 0.003), which remained significant after correction for multiple testing. However, this association was no longer significant after accounting for population stratification (p = 0.088). CONCLUSION: In this study, rare functional variants were found in the NOTCH1 gene in a French Canadian population of patients with severe tricuspid AS. This also suggests, for the first time, the presence of a common polymorphism in this gene conferring susceptibility to AS.
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Estenosis de la Válvula Aórtica/genética , Calcinosis/genética , Receptor Notch1/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Válvula Aórtica/patología , Canadá , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Lactante , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Índice de Severidad de la Enfermedad , Población Blanca/genética , Adulto JovenRESUMEN
The mechanisms modulated by periodontal pathogens in atherosclerosis are not fully understood. Aim: to perform an integrative analysis of gene and protein expression modulated by periodontal pathogens in cells and animal models for atherosclerosis. Methods: Cochrane, PRISMA and AMSTAR2 guidelines for systematic reviews were followed. Data search was conducted in Pub-med, LILACS and Science Direct databases. Gene and protein expression data were collected from the included papers to perform an overrepresentation analysis using the Reactome Pathway Analysis tool and the KEGG database. Results: Thirty-two papers were included in the review, they analyzed the effect of Fusobacterium nucleatum, Porphyromonas gingivalis, Streptococcus anginosus, Streptococcus sanguinis, Tannerella forsythia, and Treponema denticola or/and their virulent factors on gene and protein expression in human cells and animal models of atherosclerosis. Some of the modulated pathways include the immune system, programmed cell death, cellular responses to external stimuli, transport of small molecules, and signal transduction (p < 0.05). Those pathways are known to be involved in different stages of atherosclerosis progression. Conclusion: Based on the performed analysis, it is possible to state that periodontal pathogens have the potential to be a contributing factor for atherosclerosis even in absence of a high-fat diet or high shear stress.
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Text mining enables search, extraction, categorisation and information visualisation. This study aimed to identify oral manifestations in patients with COVID-19 using text mining to facilitate extracting relevant clinical information from a large set of publications. A list of publications from the open-access COVID-19 Open Research Dataset was downloaded using keywords related to oral health and dentistry. A total of 694,366 documents were retrieved. Filtering the articles using text mining yielded 1,554 oral health/dentistry papers. The list of articles was classified into five topics after applying a Latent Dirichlet Allocation (LDA) model. This classification was compared to the author's classification which yielded 17 categories. After a full-text review of articles in the category "Oral manifestations in patients with COVID-19", eight papers were selected to extract data. The most frequent oral manifestations were xerostomia (n = 405, 17.8%) and mouth pain or swelling (n = 289, 12.7%). These oral manifestations in patients with COVID-19 must be considered with other symptoms to diminish the risk of dentist-patient infection.
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COVID-19 , Envío de Mensajes de Texto , Humanos , Minería de DatosRESUMEN
Calcific aortic valve disease (CAVD) is a disorder related to progressive mineralization of valvular tissue that is a leading cause of heart disease. Thus far, there is no medical treatment to prevent the mineralization of aortic valves. It is generally thought that pathologic mineralization is linked to apoptosis of vascular cells. However, the role of apoptosis during mineralization as well as the survival signals for valvular interstitial cells (VICs), the main cellular component of aortic valves, remains to be identified. Here, through several lines of evidence, we show that bioavailability of extracellular ATP is a signal which determines survival or apoptosis of VICs and, in doing so, plays a major role in the development of CAVD. Specifically, in CAVD and in VIC cultures undergoing mineralization, we found a high level of the ectonucleotidase ENPP1. In addition, a genetic polymorphism in the intron 9 of the ENPP1 gene was associated with CAVD in a case-control cohort as well as with mRNA expression levels of ENPP1 in aortic valves. A high level of ENPP1 in CAVD promoted apoptosis-mediated mineralization of VICs by depleting the extracellular pool of ATP. We then documented that release of ATP by VICs promoted cell survival via the P2Y(2) receptor and the PI3K/Akt signaling pathway. Hence, our results show that level of ENPP1 modulates extracellular concentration of ATP, which is an important survival signal for VICs. These findings may help to develop novel pharmacological treatment for CAVD.
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Adenosina Trifosfato/fisiología , Válvula Aórtica/patología , Calcinosis/metabolismo , Cardiomiopatías/metabolismo , Células Epiteliales/metabolismo , Hidrolasas Diéster Fosfóricas/genética , Pirofosfatasas/genética , Adenosina Trifosfato/metabolismo , Válvula Aórtica/metabolismo , Apoptosis , Calcinosis/patología , Cardiomiopatías/patología , Estudios de Casos y Controles , Células Cultivadas , Perfilación de la Expresión Génica , Estudios de Asociación Genética , Humanos , Análisis de Secuencia por Matrices de Oligonucleótidos , Fosfatos/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Hidrolasas Diéster Fosfóricas/metabolismo , Polimorfismo de Nucleótido Simple , Pirofosfatasas/metabolismo , Receptores Purinérgicos P2X/genética , Receptores Purinérgicos P2X/metabolismo , Receptores Purinérgicos P2Y/genética , Receptores Purinérgicos P2Y/metabolismo , Transducción de Señal , Proteínas Cotransportadoras de Sodio-Fosfato de Tipo III/genética , Proteínas Cotransportadoras de Sodio-Fosfato de Tipo III/metabolismo , Análisis de Matrices TisularesRESUMEN
It has been hypothesised that oral bacteria can migrate, through the blood, from the mouth to the arterial plaques, thus exacerbating atherosclerosis. This study compared bacteria present in the peripheral blood of individuals with and without coronary artery disease (CAD). RNA sequences obtained from blood were downloaded from GEO (GSE58150). Eight patients with coronary artery calcification (CAC) scoring > 500 and eight healthy individuals were analysed. After conducting quality control, the sequences were aligned to the hg38 reference genome using Hisat2. Bacterial taxa were analysed by inputting the unmapped sequences into Kraken. Ecological indices were calculated using Vegan. The package DESeq2 was used to compare the counts of bacteria per standard rank between groups. A total of 51 species were found only in patients with CAD and 41 were exclusively present in healthy individuals. The counts of one phylum, one class, three orders, two families and one genus were significantly different between the analysed groups (p < 0.00032, FDR < 10%), including the orders Cardiobacteriales, Corynebacteriales and Fusobacteriales. Twenty-three bacterial species belonging to the subgingival plaque bacterial complexes were also identified in the blood of individuals from both the groups; Fusobacterium nucleatum was significantly less frequent in patients with CAD (p = 0.0012, FDR = 4.8%). Furthermore, the frequency of another 11 bacteria differed significantly among patients with CAD than that among healthy individuals (p < 0.0030, FDR < 10%). These bacteria have not been previously reported in patients with atherosclerosis and periodontitis. The presence of members of the subgingival plaque bacterial complexes in the blood of patients with CAC supports the hypothesis that the periodontopathogens can be disseminated through the blood flow to other body parts where they may enhance inflammatory processes that can lead to the development or exacerbation of atherosclerosis.
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Sangre/microbiología , Enfermedad de la Arteria Coronaria/microbiología , Placa Dental/microbiología , Enfermedades Periodontales/complicaciones , Estudios de Casos y Controles , Femenino , Humanos , Persona de Mediana Edad , Enfermedades Periodontales/microbiologíaRESUMEN
BACKGROUND: Calcific aortic valve stenosis (CAVS) is a fatal disease and there is no pharmacological treatment to prevent the progression of CAVS. This study aims to identify genes potentially implicated with CAVS in patients with congenital bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV) in comparison with patients having normal valves, using a knowledge-slanted random forest (RF). RESULTS: This study implemented a knowledge-slanted random forest (RF) using information extracted from a protein-protein interactions network to rank genes in order to modify their selection probability to draw the candidate split-variables. A total of 15,191 genes were assessed in 19 valves with CAVS (BAV, n = 10; TAV, n = 9) and 8 normal valves. The performance of the model was evaluated using accuracy, sensitivity, and specificity to discriminate cases with CAVS. A comparison with conventional RF was also performed. The performance of this proposed approach reported improved accuracy in comparison with conventional RF to classify cases separately with BAV and TAV (Slanted RF: 59.3% versus 40.7%). When patients with BAV and TAV were grouped against patients with normal valves, the addition of prior biological information was not relevant with an accuracy of 92.6%. CONCLUSION: The knowledge-slanted RF approach reflected prior biological knowledge, leading to better precision in distinguishing between cases with BAV, TAV, and normal valves. The results of this study suggest that the integration of biological knowledge can be useful during difficult classification tasks.
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This study analyzed the expression of extracellular matrix (ECM) proteins during aortic valve calcification with mass spectrometry, and further validated in an independent human cohort using RNAseq data. The study reveals that valve calcification is associated with significant disruption in ECM and metabolic pathways, and highlights a strong connection between metabolic markers and ECM remodeling. It also identifies FNDC1 and MXRA5 as novel ECM biomarkers in calcified valves, electing them as potential targets in the development and progression of aortic stenosis.
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OBJECTIVE: The objective of this study was to compare the ICDAS-II caries status and caries-related factors among children from rural and urban schools in Pasto, Colombia. MATERIALS AND METHODS: The study included 120 children (4 - 6 year- old children) from rural (privileged) and urban (unprivileged) schools. Caries was evaluated using the ICDAS-II criteria. A survey about the factors related to the presence of caries was applied. Chi-square and Fisher's tests were used to assess the differences in each study variable between the two groups. A Mann-Whitney U test was used to compare the number of teeth, per ICDAS-II category, between the groups. Negative binomial regression was used to estimate the percentage change in the mean number of teeth, per ICDAS-II category, among the rural and urban students. RESULTS: Significant differences were found between the rural and urban students for the ICDAS-II 0 and 3-6 categories (p<0.001). The mean number of teeth with moderate-to-severe caries status increased 233% in children from the rural school compared to those attending the urban school (p=0.0). Toothbrushing frequency (p=0.006), cariogenic diet, time elapsed from last dental visit, socioeconomic status, and type of health regime (p<0.001) were among the significant factors related to the rural and urban schools. CONCLUSIONS: This was the first study to compare ICDAS-II caries status between rural and urban students in Colombia. A worse caries status was found in rural students. This study identified the socioeconomic and clinical factors to guide specific interventions for rural children by modifying the available oral health promotion and disease prevention programs.
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BACKGROUND: Calcific aortic valve stenosis (AS) is a life-threatening disease with no medical therapy. The genetic architecture of AS remains elusive. This study combines genome-wide association studies, gene expression, and expression quantitative trait loci mapping in human valve tissues to identify susceptibility genes of AS. METHODS AND RESULTS: A meta-analysis was performed combining the results of 2 genome-wide association studies in 474 and 486 cases from Quebec City (Canada) and Paris (France), respectively. Corresponding controls consisted of 2988 and 1864 individuals with European ancestry from the database of genotypes and phenotypes. mRNA expression levels were evaluated in 9 calcified and 8 normal aortic valves by RNA sequencing. The results were integrated with valve expression quantitative trait loci data obtained from 22 AS patients. Twenty-five single-nucleotide polymorphisms had P<5×10(-6) in the genome-wide association studies meta-analysis. The calcium signaling pathway was the top gene set enriched for genes mapped to moderately AS-associated single-nucleotide polymorphisms. Genes in this pathway were found differentially expressed in valves with and without AS. Two single-nucleotide polymorphisms located in RUNX2 (runt-related transcription factor 2), encoding an osteogenic transcription factor, demonstrated some association with AS (genome-wide association studies P=5.33×10(-5)). The mRNA expression levels of RUNX2 were upregulated in calcified valves and associated with eQTL-SNPs. CACNA1C encoding a subunit of a voltage-dependent calcium channel was upregulated in calcified valves. The eQTL-SNP with the most significant association with AS located in CACNA1C was associated with higher expression of the gene. CONCLUSIONS: This integrative genomic study confirmed the role of RUNX2 as a potential driver of AS and identified a new AS susceptibility gene, CACNA1C, belonging to the calcium signaling pathway.
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Estenosis de la Válvula Aórtica , Válvula Aórtica/patología , Calcinosis , Canales de Calcio Tipo L , Señalización del Calcio/genética , Subunidad alfa 1 del Factor de Unión al Sitio Principal , Bases de Datos Genéticas , Polimorfismo de Nucleótido Simple , Válvula Aórtica/metabolismo , Estenosis de la Válvula Aórtica/genética , Estenosis de la Válvula Aórtica/metabolismo , Calcinosis/genética , Calcinosis/metabolismo , Canales de Calcio Tipo L/genética , Canales de Calcio Tipo L/metabolismo , Estudios de Casos y Controles , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Femenino , Estudio de Asociación del Genoma Completo , Humanos , MasculinoRESUMEN
BACKGROUND: The biological functions of epicardial adipose tissue (EAT) remain largely unknown. However, the proximity of EAT to the coronary arteries suggests a role in the pathogenesis of coronary artery disease (CAD). The objectives of this study were to identify genes differentially regulated among three adipose tissues, namely EAT, mediastinal (MAT) and subcutaneous (SAT) and to study their possible relationships with the development of cardiovascular diseases. METHODS AND RESULTS: Samples were collected from subjects undergoing coronary artery bypass grafting surgeries. Gene expression was evaluated in the three adipose depots of six men using the Illumina® HumanWG-6 v3.0 expression BeadChips. Twenty-three and 73 genes were differentially up-regulated in EAT compared to MAT and SAT, respectively. Ninety-four genes were down-regulated in EAT compared to SAT. However, none were significantly down-regulated in EAT compared to MAT. More specifically, the expression of the adenosine A1 receptor (ADORA1), involved in myocardial ischemia, was significantly up-regulated in EAT. Levels of the prostaglandin D2 synthase (PTGDS) gene, recently associated with the progression of atherosclerosis, were significantly different in the three pairwise comparisons (EAT>MAT>SAT). The results of ADORA1 and PTGDS were confirmed by quantitative real-time PCR in 25 independent subjects. CONCLUSIONS: Overall, the transcriptional profiles of EAT and MAT were similar compared to the SAT. Despite this similarity, two genes involved in cardiovascular diseases, ADORA1 and PTGDS, were differentially up-regulated in EAT. These results provide insights about the biology of EAT and its potential implication in CAD.
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Tejido Adiposo/metabolismo , Enfermedad de la Arteria Coronaria/etiología , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Oxidorreductasas Intramoleculares/genética , Lipocalinas/genética , Receptor de Adenosina A1/genética , Tejido Adiposo/patología , Anciano , Enfermedad de la Arteria Coronaria/genética , Perfilación de la Expresión Génica/métodos , Humanos , Masculino , Mediastino/patología , Persona de Mediana Edad , Pericardio/metabolismo , Pericardio/patología , Grasa Subcutánea/metabolismo , Grasa Subcutánea/patologíaRESUMEN
Only a handful of studies have attempted to unravel the genetic architecture of calcific aortic valve stenosis (AS). The goal of this study was to validate genes previously associated with AS. Seven genes were assessed: APOB, APOE, CTGF, IL10, PTH, TGFB1, and VDR. Each gene was tested for a comprehensive set of single-nucleotide polymorphisms (SNPs). SNPs were genotyped in 457 patients who underwent surgical aortic valve replacement, and allele frequencies were compared to 3,294 controls. A missense mutation in the APOB gene was significantly associated with AS (rs1042031, E4181K, p = 0.00001). A second SNP located 5.6 kilobases downstream of the APOB stop codon was also associated with the disease (rs6725189, p = 0.000013). Six SNPs surrounding the IL10 locus were strongly associated with AS (0.02 > p > 6.2 × 10⻹¹). The most compelling association for IL10 was found with a promoter polymorphism (rs1800872) well known to regulate the production of the encoded anti-inflammatory cytokine. The frequency of the low-producing allele was greater in cases compared to controls (30% vs 20%, p = 6.2 × 10⻹¹). SNPs in PTH, TGFB1, and VDR had nominal p values <0.05 but did not resist Bonferroni correction. In conclusion, this study suggests that subjects carrying specific polymorphisms in the IL10 and APOB genes are at higher risk for developing AS.
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Estenosis de la Válvula Aórtica/genética , Anciano , Apolipoproteínas B/genética , Apolipoproteínas E/genética , Estudios de Casos y Controles , Factor de Crecimiento del Tejido Conjuntivo/genética , Femenino , Frecuencia de los Genes , Genotipo , Heterocigoto , Humanos , Interleucina-10/genética , Masculino , Mutación Missense , Hormona Paratiroidea/genética , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas , Receptores de Calcitriol/genética , Índice de Severidad de la Enfermedad , Factor de Crecimiento Transformador beta1/genéticaRESUMEN
Con el objetivo de estimar la diversidad, la estructura y el flujo génico de tres poblaciones afrodescendientes del suroccidente colombiano (Buenaventura, Mulaló y Tumaco), se analizaron los alelos revelados por ocho STR’s autosómicos en 78 indi-viduos no relacionados, mediante amplificación por PCR y comparación con escaleras alélicas de cada sistema corridas en geles de poliacrilamida al 8%. Los resultados se compararon con las poblaciones amerindias Awa-Kuaikier y Coyaima, y las mestizas del Valle del Cauca y de Cauca. Se encontró que las muestras afrodescendientes y amerindias fueron moderadamente diversas (h entre 0,768±0,414 y 0,796±0,424), mientras que las mestizas mostraron índices mayores (>0,803), lo que puede ser consecuencia del mestizaje con amerindios, el cual puede explicar la alta endogamia observada para éstas. El AMOVA exhibió estructuración moderada entre las poblaciones afrodescendientes (FST= 0,098; p<0,05), y alta entre los tres grupos étnicos comparados (FST=0,26723; p<0,05). Las distancias genéticas favorecieron la cercanía entre Tumaco y Buenaventura, soportada por la tasa de migración encontrada (34,298), al igual que al interior de las poblaciones amerindias y mestizas. Las diferencias observadas entre Mulaló y las otras poblaciones negras quizá se expliquen porque es un aislado poblacional más cerrado. El árbol NJ mostró la relación más cercana entre las poblaciones amerindias y mestizas, además del carácter ancestral de las afrodescendientes. Esto sustenta la idea del flujo genético mantenido entre las tres etnias, principalmente entre las poblaciones amerindias y mestizas analizadas, soportado por las distancias genéticas, las tasas de migración y la matrilinealidad amerindia reportada en la literatura.
To estimate the diversity, structure and genetic flow in three colombian southwest afrodescendent populations (Buenaventura, Mulaló y Tumaco), the alleles revealed by 8 autosomal STR’s were analyzed in 78 no related individuals, by the use of PCR and comparison with specific allelic ladders for every system resolved by polyacrylamide gel (8%). The results were compared with 2 amerindian populations (Awa-Kuaikier and Coyaima) and 2 mixed colombian populations (Valle del Cauca and Cauca). For the afrodescendent and amerindian populations was found moderate diversity (h between 0.768±0.414 and 0.796±0.424), in contrast, the mixed population showed higher rates (>0.803), which is probably caused by mixing with amerindians, that also can explain the high endogamy seen in mixed populations. The AMOVA exhibited moderate genetic structure between the afrodescendent populations (FST= 0.098; p<0.05), but higher between the three ethnical groups compared (FST=0.26723; p<0.05). The closer genetics distances are in favor of Tumaco and Buenaventura, supported for the migration rate found (34.298), which was the same inside of amerindian and mixed populations. Maybe, because Mulaló is a closed isolated population, its differences in front others afrodescendent populations are explained. The neighbor-joining tree showed nearest relations among amerindian and mixed populations, furthermore, the ancestral character for the afrodescendents. That sustains the idea of genetic flow maintained between the 3 ethnical groups, principally between amerindian and mixed populations, supported because the genetic differences, migration rates and amerindian matrilineality reported in the literature.