81 research outputs found
Genes and Coronary Artery Disease Where Are We?
No full textSusceptibility to coronary artery disease (CAD) is claimed to be 40% to 60% inherited, but until recently genetic risk factors predisposing to CAD have been elusive. Comprehensive prevention of CAD requires manipulation of genetic risk. The availability of microarrays of single-nucleotide polymorphisms enabling genome-wide association studies (GWAS) led to the discovery of 33 genetic risk variants for CAD. Surprisingly, 23 risk variants mediate their risk through unknown mechanisms, with only 10 associating with hypertension or lipids. Thus, there are several mechanisms contributing to the pathogenesis of CAD yet to be elucidated. The first risk variant discovered by GWAS was 9p21.3, which occurs in 75% of all populations except African, with a mean increased risk of 25% per copy. Of the 33 variants for CAD, the increased risk varies from 6% to 92% with a mean increased risk of 18%, occurring on average in 47% of the population. The maximum number of risk alleles per individual would be 66. In the CARDIoGRAM (Coronary Artery Disease Genome-wide Replication and Meta Analysis) study of 23 variants, the average per individual was 17, the minimum 7, and the maximum 37. The top 10th percentile has an odds ratio of 1.88 and the lowest percentile an odds ratio of 0.55. Routine genetic screening is unlikely until management is improved by genetic testing. Risk variants should provide pathophysiological insights and targets for novel therapy. While risk variants are less potent predictors of CAD, compared with biomarkers, they have the advantage of not changing in one's lifetime and are unaffected by diet, sex, age, or medication
Genomics in Cardiovascular Disease
No full textA paradigm shift toward biology occurred in the 1990s and was subsequently catalyzed by the sequencing of the human genome in 2000. The cost of deoxyribonucleic acid (DNA) sequencing has gone from millions to thousands of dollars with sequencing of one's entire genome costing only $1,000. Rapid DNA sequencing is being embraced for single gene disorders, particularly for sporadic cases and those from small families. Transmission of lethal genes such as associated with Huntington's disease can, through in vitro fertilization, avoid passing it on to one's offspring. DNA sequencing will meet the challenge of elucidating the genetic predisposition for common polygenic diseases, especially in determining the function of the novel common genetic risk variants and identifying the rare variants, which may also partially ascertain the source of the missing heritability. The challenge for DNA sequencing remains great, despite human genome sequences being 99.5% identical, the 3 million single nucleotide polymorphisms responsible for most of the unique features add up to 40 to 60 new mutations per person which, for 7 billion people, is 300 to 400 billion mutations. It is claimed that DNA sequencing has increased 10,000-fold while information storage and retrieval only 16-fold. The physician and health user will be challenged by the convergence of 2 major trends, whole genome sequencing, and the storage/retrieval and integration of the data
Recent success in the discovery of coronary artery disease genes
No full text For more than 50 years, epidemiological studies have indicated that genetic predisposition accounts for approximately 50% of the susceptibility to coronary artery disease (CAD) and its sequelae, including myocardial infarction. Since common diseases such as CAD are caused by multiple genes, the age-old method of linkage analysis used to map monogenic Mendelian disorders in families unfortunately lacks the required sensitivity. The technology to identify genes predisposing individuals to CAD and other common diseases did not become available until 2005. This technology provided computerized arrays containing hundreds of thousands of DNA markers in the form of single-nucleotide polymorphisms (SNPs). This made it possible to pursue an unbiased approach referred to as genome-wide association studies. The first gene for CAD was simultaneously identified by 2 independent groups in 2007. In a very short interval, a total of 23 loci were mapped that were linked to increased risk for CAD. The results of these studies confirm that CAD is caused by multiple genes, each contributing minimal risk. The most exciting and novel findings are that these loci do not act through known risk factors for CAD and that the loci are more likely to be in DNA regions that regulate transcription rather than being in coding regions for protein. </jats:p
Efetividade de antissépticos bucais na prevenção da colonização bacteriana em pacientes com braquetes ortodônticos
Get PDFTCC (graduação) - Universidade Federal de Santa Catarina. Centro de Ciências da Saúde. Odontologia.Vários estudos comprovam que a placa bacteriana (PB) constitui um importante fator etiológico para a doença cárie e periodontal. Além da correta higienização bucal que induz a desorganização da PB, diversos estudos vem comprovando que o uso de antissépticos bucais é um importante aliado na prevenção destas afecções, em especial, em pacientes portadores de braquetes ortodônticos (CARVALHO; MALTZ, 1997; SBORDONE; BORTOLAIA, 2003; MARSH; NYVADE, 2003). Esses antissépticos bucais são substâncias químicas que apresentam ação antimicrobiana e são utilizados para complementação à prevenção mecânica da formação da PB. Na cavidade oral, estima-se que exista aproximadamente entre 550 a 600 espécies bacterianas, sendo de fundamental importância a manutenção de uma homeostase microbiológica. Esse estudo objetivou determinar a efetividade do uso de antissépticos bucais na prevenção da colonização bacteriana em pacientes que fazem uso de aparatologia fixa, já que esses, são pacientes de alto risco a cárie. Foram testados, escolheu-se dois enxaguantes bucais, Colgate Plax® e Oral B® que tiveram seus resultados comparados ao Grupo controle que fez uso de uma solução Placebo. As amostras foram recolhidas três vezes, em três intervalos de tempos diferentes: tempo 0 (antes do início do tratamento), após 15 dias de uso das soluções (tempo T1) e após 30 dias de uso das soluções escolhidas (tempo T2). Após a retirada dos braquetes, estes foram depositados em eppendorfs contando solução salina estéril. O conteúdo dos mesmos foi submetido a uma série de diluições sucessivas e uma alíquota de cada diluição foi plaqueada, em placas de Petri contendo aproximadamente 20 ml de ágar MH. As placas foram mantidas em incubadora bacteriológica a 37°C por 24h e as colônias presentes em cada placa foram enumeradas por observação macroscópica. A análise dos resultados obtidos indica que os enxaguantes bucais são efetivos na inibição da colonização bacteriana das borrachas presentes no braquetes ortodônticos, tendo o Colgate Plax® apresentado os melhores índices de resposta, com um índice de inibição bacteriana em torno de 71% (T1) e 80% (T2) seguido do Oral B® com 63% (T1) e 67% (T2). Os resultados não puderam ser analisados estatisticamente devido ao pequeno número de pacientes participantes da pesquisa, em decorrência dos altos custos dos materiais necessários
Interferon-γ Activates Expression of p15 and p16 Regardless of 9p21.3 Coronary Artery Disease Risk Genotype
No full textObjectivesBecause post-transcriptional mechanisms modulate levels of p16 (encoded by CDKN2A) and p15 (encoded by CDKN2B), we tested whether interferon-γ regulates the expression of these proteins and the effect of the 9p21 genotype.BackgroundThe mechanism whereby the common variant at chromosome 9p21.3 confers risk for coronary artery disease (CAD) remains uncertain. A recent report proposed that 9p21.3 confers differential activation of adjacent genes in response to interferon-γ, and reported that mRNA levels of CDKN2B are reduced in response to interferon-γ.MethodsHuman umbilical vein endothelial cells (HUVECs), aortic smooth muscle cells, HeLa cells, HEK293 cells, and 16 human lymphoblastoid cell lines, all genotyped for the 9p21.3 locus, were treated with interferon-γ and analyzed by immunoblot.ResultsIn all cells tested—except HUVECs where expression was not modulated by interferon-γ—regardless of 9p21.3 genotype, interferon-γ increased the expression of p16 and p15. Northern blot analysis confirmed that interferon-γ has little effect on mRNA levels of CDKN2A and CDKN2B.ConclusionsThe 9p21.3 risk genotype does not affect the activation of cyclin-dependent kinase inhibitors p15 and p16 by interferon-γ. Thus, another mechanism is likely to account for the CAD risk associated with this locus
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