• In 2009, Sharpless and his team were the first to discover altered human INK4/ARF expression as the mechanism for the 9p21.3 genetic risk allele of atherosclerosis. (wikipedia.org)
  • This was first published study identifying the underlying mechanism of 9p21.3, a genetic risk variant with the strongest, and most consistent association with atherosclerosis in multiple, independent, large-scale GWASs (Genome Wide Association Studies). (wikipedia.org)
  • The findings remain to be the most plausible mechanism of 9p21.3 atherosclerosis risk up to this date. (wikipedia.org)
  • All studies reported a strong association of a region of elevated linkage disequilibrium (LD) on human chromosome 9p21.3 with CHD. (biomedcentral.com)
  • Sequence variants on chromosome 9p21.3 confer risk for atherosclerotic stroke. (nature.com)
  • The chromosome 9p21.3 coronary heart disease risk allele is associated with altered gene expression in normal heart and vascular tissues. (cdc.gov)
  • A recent genome-wide association study of intracranial aneurysms in Finnish, Dutch and Japanese cohorts totaling 5,891 cases and 14,181 controls identified three new loci strongly associated with intracranial aneurysms on chromosomes 18q11.2 and 10q24.32, and replicated two previously found loci on chromosomes 8q11.23-q12.1 and 9p21.3. (biomedcentral.com)
  • Conducting studies in mice with atherosclerosis, the researchers showed that loss of a candidate gene at this locus leads to impaired "efferocytosis" - from the Latin for "take to the grave" - the process by which dead or necrotic cells are removed. (stanford.edu)
  • If you were born with genetic variation at the 9p21 locus, your risk of heart disease is elevated, though we haven't understood why. (stanford.edu)
  • Interestingly, comparative mapping revealed that the Athsq1 congenic interval contains the mouse region homologous to a widely-replicated CHD locus on human chromosome 9p21. (scite.ai)
  • We replicated previous associations for cardioembolic stroke near PITX2 and ZFHX3 and for large vessel stroke at a 9p21 locus. (nature.com)
  • In a cross-sectional analysis, genome-wide association study of estimates of mCA expansion rate identified TCL1A , NRIP1 , and TERT locus variants as modulators of mCA clonal expansion rate. (bvsalud.org)
  • Objective-Susceptibility to atherosclerosis is genetically complex, and modifier genes that do not operate via traditional risk factors are largely unknown. (scite.ai)
  • Methods and Results-We previously identified atherosclerosis susceptibility QTL (Athsq1) on chromosome 4 acting independently of systemic risk factors. (scite.ai)
  • The current research is aimed at assessing the correlation between two functional GAS5 variants (rs145204276 and rs55829688) and susceptibility to IS in a Han Chinese population. (hindawi.com)
  • In addition, a number of different genetic determinants of IS risk have been identified in genome-wide association studies, with single-nucleotide polymorphisms (SNPs) in 9p21, PITX2, HDAC9, ABO, NINJ2, ALDH2, and TSPAN2, all being linked with stroke susceptibility [ 2 ]. (hindawi.com)
  • The association of the 4q25 susceptibility variant for atrial fibrillation with stroke is limited to stroke of cardioembolic etiology. (nature.com)
  • The cholesteryl ester transfer protein (CETP) has a central role in the lipid metabolism and therefore may alter the susceptibility to atherosclerosis. (biomedcentral.com)
  • To identify common variants contributing to normal variation in two specific domains of cognitive functioning, we conducted a genome-wide association study (GWAS) of executive functioning and information processing speed in non-demented older adults from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) consortium. (escholarship.org)
  • In other words, a commonly inherited genetic variant, which is found in 20 percent of the population, contributes to the development of coronary artery disease (also known as coronary atherosclerosis) by stimulating the accumulation of necrotic debris within the evolving plaque. (stanford.edu)
  • Coronary atherosclerosis is the process by which plaque builds up in the wall of heart vessels, eventually leading to chest pain and potentially lethal heart attacks. (stanford.edu)
  • Advances in our knowledge about the workings of genes and their variants coupled with technological advances in analysing the genome along with improved bioinformatics has enabled greater understanding of the underlying molecular aetiology of ischaemic stroke. (bmj.com)
  • Recent progress over the last two decades in the field of molecular genetics, especially with new tools such as genome-wide association studies, has helped to identify new genes and their variants, which can be used for calculations of risk, prediction of treatment efficacy, or detection of subjects prone to drug side effects. (mdpi.com)
  • Early studies used the candidate gene approach to identify rare genetic variants contributing to traditional risk factors including plasma levels of LDL/VLDL, HDL, lipoprotein (a), homocysteine, and blood pressure. (scite.ai)
  • GAS5 is found on chromosome 1q25.1, with the gene containing 12 exons across a 4.087 kb region, coding for 29 different GAS5 splicing variants [ 11 ]. (hindawi.com)
  • The association of ACE I/D gene polymorphism with severe carotid atherosclerosis in patients undergoing carotid endarterectomy. (cdc.gov)
  • The candidate gene approach focuses on the search for an association between T2DM and sequence variants in or near biologically defined candidate genes which have been chosen based on their known physiological function. (scialert.net)
  • A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele). (nih.gov)
  • The CETP gene is located on chromosome 16q21. (biomedcentral.com)
  • Widely studied CETP variants is a silent base change called the Thermobius aquaticus IB (TaqIB) affecting the 277th nucleotide in the first intron of the CETP gene [ 18 ]. (biomedcentral.com)
  • Rs17518584 is located about 170 kb upstream of the transcription start site of the major transcript for the CADM2 gene, but is within an intron of a variant transcript that includes an alternative first exon. (escholarship.org)
  • Risk variants for atrial fibrillation on chromosome 4q25 associate with ischemic stroke. (nature.com)
  • A sequence variant in ZFHX3 on 16q22 associates with atrial fibrillation and ischemic stroke. (nature.com)
  • Leeper, a physician and assistant professor of vascular surgery, and colleagues Yoko Kojima, MD, Tom Quertermous , MD, and others set out to discover why genetic variation at the chromosome 9p21 location has been repeatedly identified as the most important commonly inherited DNA sequence for a wide range of cardiovascular diseases including stroke, heart attacks and aneurysms. (stanford.edu)
  • New approaches, including identification of causal variants, rare variants and copy number variants, such as insertions and deletions, may improve genetic risk prediction for SAH and intracranial aneurysms. (biomedcentral.com)
  • For presence of aneurysms, atherosclerosis, a familial preponderance and polycystic kidney disease are the main risk factors. (biomedcentral.com)
  • Additional stratification conforming to IS subtypes exhibited that individuals carrying the rs145204276 del allele conferred a higher risk of expanding a larger artery atherosclerosis stroke subset. (hindawi.com)
  • Evidence continues to accumulate to suggest important roles for inflammation and genetic factors in the process of atherosclerosis and specifically in stroke. (medscape.com)
  • For example, serum biomarkers, such as high sensitivity C-reactive protein (hsCRP) and cytokine levels, predict progression of atherosclerosis and risk of stroke. (medscape.com)
  • In 2010 Sharpless's lab reported the first known human circular RNA produced from a long non-coding RNA, and linked its expression to alleles strongly associated with risk of atherosclerosis. (wikipedia.org)
  • You can be a non-smoker, be thin, have low blood pressure, and still be at risk for a heart attack if you were born with this variant. (stanford.edu)
  • Our study supports a model wherein the rs145204276 variant in the GAS5 lncRNA is associated with IS risk, thus representing a potentially viable biomarker for IS prevention and treatment. (hindawi.com)
  • T2DM is a complex trait where common genetic variants having modest individual effects act together and interact with environmental factors to modulate the risk of the disease. (scialert.net)
  • In addition, the finding in the stage 1 sample that AD risk is significantly influenced by the interaction of APOE with rs1595014 in TMEM106B (P=1·6 × 10(-7)) is noteworthy, because TMEM106B variants have previously been associated with risk of frontotemporal dementia. (escholarship.org)
  • First, molecular events in T2DM pathogenesis have been examined directly by testing the role of sequence variants of specific candidate genes. (scialert.net)
  • According to the current paradigm, atherosclerosis is not a bland cholesterol storage disease, as previously thought, but a dynamic, chronic, inflammatory condition due to a response to endothelial injury. (medscape.com)
  • Analysis of extracellular matrix composition revealed prominent accumulation of versican, a presumed proatherogenic matrix component abundant in human lesions but almost absent in the widely-used C57BL/6 murine atherosclerosis model. (scite.ai)
  • Serum levels and polymorphisms of matrix metalloproteinases (MMPs) in carotid artery atherosclerosis: higher MMP-9 levels are associated with plaque vulnerability. (cdc.gov)
  • Despite extensive molecular genetics investigations, non specific reproducibly genetic variants associated with CAD were found. (biomedcentral.com)
  • Key Words: atherosclerosis Ⅲ congenic strain Ⅲ genetics Ⅲ extracellular matrix Ⅲ mapping S usceptibility to atherosclerosis is influenced by both genetic and environmental factors, with approximately 40% to 60% of interindividual variation attributed to genetic factors. (scite.ai)
  • n\nConclusion-These findings identify HDAC as a critical component of a transcriptional cascade regulating SMC proliferation and suggest that HDAC might play a pivotal role in the development of proliferative vascular diseases, including atherosclerosis and in-stent restenosis. (cret-signal.com)
  • Variants in the GAS5 promoter region have been reported to be linked to mutiple diseases. (hindawi.com)
  • This study genotyped the two GAS5 variants in 1086 IS patients as well as 1045 age-matched healthy controls by using an improved multitemperature ligase detection reaction (iMLDR-TM) genotyping technology. (hindawi.com)
  • the effect size for the rare rs3798220 variant was similar (dominant OR 1.47, 95% CI 0.81 to 2.67, p = 0.20), but power was limited to demonstrate significance. (cret-signal.com)
  • These driver mutations can be single nucleotide variants in cancer driver genes or larger structural rearrangements called mosaic chromosomal alterations (mCAs). (bvsalud.org)
  • Association of six genetic variants with myocardial infarction. (cdc.gov)
  • Several genetic studies have demonstrated an association between genetic variants in a region on chromosome 9p21 and in a region on chromosome 16q22 with myocardial infarction (MI) and atrial fibrillation (AF) accompanied by cerebral infarction (CI), respectively. (biomedcentral.com)
  • Investigation of 89 candidate gene variants for effects on all-cause mortality following acute coronary syndrome. (snpedia.com)
  • PMID 18757290 ] Associations between single nucleotide polymorphisms on chromosome 9p21 and risk of coronary heart disease in Chinese Han population. (snpedia.com)
  • Surprisingly, we showed that there was a strong influence of this genetic variation on the progression of coronary atherosclerosis, which translated into the probability of these patients undergoing new percutaneous coronary intervention or bypass surgery. (medscape.com)
  • The influence of genetic factors is greater when the coronary event occurs at a young age, so early MI is an ideal condition for assessing the role of newly discovered genetic variants associated with the disease, he explained. (medscape.com)
  • The association between the chromosome 9p21 CDKN2B-AS1 gene variants and the lipid metabolism: A pre-diagnostic biomarker for coronary artery disease. (cdc.gov)
  • New findings in the roles of Cyclin-dependent Kinase inhibitors 2B Antisense RNA 1 (CDKN2B-AS1) rs1333049 G/C and rs4977574 A/G variants on the risk to coronary heart disease. (cdc.gov)
  • RATIONALE: Human genome-wide association studies have identified genetic variants in the chromosome 9p21 region that confer increased risk of coronary artery disease and other age-related diseases. (isciii.es)
  • The risk alleles for atherosclerosis-related phenotypes were consistently associated with a lower expression of ANRIL when evaluating exons 1-2. (nih.gov)
  • To explore the mechanism of this association, we investigated whether expression of proximate transcripts (p16(INK4a), p15(INK4b), ARF, ANRIL and MTAP) correlate with genotype of representative 9p21 SNPs.We analyzed expression of 9p21 transcripts in purified peripheral blood T-cells (PBTL) from 170 healthy donors. (nih.gov)
  • Identification of eight new ANRIL splice variants. (snpedia.com)
  • Chromosome 9p21 SNPs Associated with Multiple Disease Phenotypes Correlate with ANRIL Expression. (snpedia.com)
  • Disease-Associated Risk Variants in ANRIL Are Associated with Tumor-Infiltrating Lymphocyte Presence in Primary Melanomas in the Population-Based GEM Study. (cdc.gov)
  • Interestingly, it has been reported that ANRIL is capable of forming RNA circles, and a circular isoform of ANRIL (circ_ANRIL) is associated with the development of atherosclerosis [ 9 ]. (biomedcentral.com)
  • The chromosomal region where these SNPs are located is 9p21, and has no known genes. (snpedia.com)
  • Four SNPS on chromosome 9p21 confer risk to premature, familial CAD and MI in an American Caucasian population (GeneQuest). (snpedia.com)
  • A genetic variant on chromosome 9p21 and incident heart failure in the ARIC study. (snpedia.com)
  • April 8, 2009 (Orlando, Florida) - People who suffered an early-onset MI were more likely to undergo future revascularization during 20 years of follow-up if they carried a particular genetic variant on chromosome 9p21, according to a new Italian study reported at the American College of Cardiology 2009 Scientific Sessions last week. (medscape.com)
  • None of us could believe that one single genetic variant could have such a big biological influence," said Dr Diego Ardissino (University of Parma, Italy), who presented the findings during a late-breaking clinical-trials session. (medscape.com)
  • Identification of the genetic variant could help doctors in decisions about treatment following an MI, Ardissino said. (medscape.com)
  • The first is this report that a novel genetic variant that raises some people's odds of having a heart attack has been identified. (blogspot.com)
  • The rs 1333040 variant significantly affected (p=0.01) the occurrence of cardiovascular events during follow-up, with a relative risk of 1.19 for those who were heterozygous for this risk allele and 1.41 for homozygous carriers. (medscape.com)
  • According to the current paradigm, atherosclerosis is not a bland cholesterol storage disease, as previously thought, but a dynamic, chronic, inflammatory condition due to a response to endothelial injury. (medscape.com)
  • The etiology of most chronic human diseases (such as asthma, atherosclerosis, and cancer) is complex, involving a mix of genetic and environmental factors interacting with each other over hours, days, months, or years. (blogspot.com)
  • It is still not clear which of or how these transcripts are involved in the pathogenesis of atherosclerosis. (nih.gov)
  • However, increased Ink4/Arf gene dosage did not affect atherosclerosis development in different vascular regions of both male and female apoE-/- mice fed either normal or high-fat diet. (isciii.es)