|
Hypercholesterolemia
|
0.700 |
Biomarker
|
disease |
GENOMICS_ENGLAND |
Use of low-density lipoprotein cholesterol gene score to distinguish patients with polygenic and monogenic familial hypercholesterolaemia: a case-control study.
|
23433573 |
2013 |
|
Hypercholesterolemia
|
0.700 |
Biomarker
|
disease |
HPO |
|
|
|
|
Hypercholesterolemia
|
0.700 |
GeneticVariation
|
disease |
LHGDN |
We have identified the D374Y mutant of PCSK9 in three FH families of English origin; all 12 affected individuals have unusually severe hypercholesterolaemia and require more stringent treatment than typical FH patients, who are heterozygous for defects in the LDL receptor.
|
15772090 |
2005 |
|
Hypercholesterolemia
|
0.700 |
Biomarker
|
disease |
LHGDN |
Several gain-of-function mutations in PCSK9 cause hypercholesterolemia and premature atherosclerosis, and thus, inhibition of PCSK9-induced degradation of the LDLR may be used to treat this deadly disease.
|
18799458 |
2008 |
|
Hypercholesterolemia
|
0.700 |
GeneticVariation
|
disease |
LHGDN |
A mutation in PCSK9 causing autosomal-dominant hypercholesterolemia in a Utah pedigree.
|
14727179 |
2004 |
|
Hypercholesterolemia
|
0.700 |
GeneticVariation
|
disease |
LHGDN |
By comparing the number of patients with gain-of-function mutations in PCSK9 with the number of familial hypercholesterolemia heterozygotes among subjects with hypercholesterolemia, the prevalence of subjects with gain-of-function mutations in PCSK9 in Norway can be estimated to one in 15,000.
|
18266662 |
2008 |
|
Hypercholesterolemia
|
0.700 |
GeneticVariation
|
disease |
LHGDN |
The D374Y gain-of-function mutant, associated with hypercholesterolemia and early-onset cardiovascular disease, binds the receptor 25 times more tightly than wild-type PCSK9 at neutral pH and remains exclusively in a high-affinity complex at the acidic pH.
|
17435765 |
2007 |
|
Hypercholesterolemia
|
0.700 |
Biomarker
|
disease |
CTD_human |
Mutations in PCSK9 cause autosomal dominant hypercholesterolemia.
|
12730697 |
2003 |
|
Hypercholesterolemia
|
0.700 |
Biomarker
|
disease |
BEFREE |
Given that new onset diabetes mellitus (NODM) and worsening of glucose control in patients with established type 2 diabetes mellitus (T2DM) is related to low density lipoprotein cholesterol (LDL-C) reduction, it would be of great interest to investigate if this is also the case for proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, which have recently be licensed for the treatment of hypercholesterolaemia.
|
28128061 |
2017 |
|
Hypercholesterolemia
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Logistic regression analysis showed a trend of association between PCSK9 E670G and hypercholesterolemia after adjustment for covariates (P = .059).
|
24793346 |
2015 |
|
Hypercholesterolemia
|
0.700 |
Biomarker
|
disease |
BEFREE |
Proprotein convertase subtilisin/kexin type 9 (PCSK9) decreases low-density lipoprotein (LDL) clearance, promotes hypercholesterolemia, and has recently emerged as a novel therapeutic target.
|
26824363 |
2016 |
|
Hypercholesterolemia
|
0.700 |
AlteredExpression
|
disease |
BEFREE |
Elevated plasma PCSK9 level is equally detrimental for patients with nonfamilial hypercholesterolemia and heterozygous familial hypercholesterolemia, irrespective of low-density lipoprotein receptor defects.
|
24632287 |
2014 |
|
Hypercholesterolemia
|
0.700 |
Biomarker
|
disease |
BEFREE |
LDL cholesterol (LDL-C) lowering drugs that operate through the inhibition of PCSK9 are being pursued for the management of hypercholesterolemia and reducing its associated atherosclerotic cardiovascular disease (CVD) risk.
|
30448414 |
2019 |
|
Hypercholesterolemia
|
0.700 |
Biomarker
|
disease |
BEFREE |
In more than 80% of those with a clinical diagnosis of FH but with no detectable mutation in LDLR/APOB/PCSK9, the polygenic explanation is the most likely for their hypercholesterolaemia.
|
30270085 |
2018 |
|
Hypercholesterolemia
|
0.700 |
AlteredExpression
|
disease |
BEFREE |
This review will address the biochemical, genetic, and clinical aspects associated with PCSK9's biology and pathophysiology in cells, rodent and human, with emphasis on the clinical benefits of silencing the expression/activity of PCSK9 as a new modality in the treatment of hypercholesterolemia and associated pathologies.
|
24625727 |
2014 |
|
Hypercholesterolemia
|
0.700 |
Biomarker
|
disease |
BEFREE |
Conversely, Pod-ATTAC mice and NTS-treated mice showed hypercholesterolemia and a 7- to 24-fold induction in plasma PCSK9.
|
27358438 |
2016 |
|
Hypercholesterolemia
|
0.700 |
Biomarker
|
disease |
BEFREE |
Effect of PCSK9 Inhibitors on Clinical Outcomes in Patients With Hypercholesterolemia: A Meta-Analysis of 35 Randomized Controlled Trials.
|
29223954 |
2017 |
|
Hypercholesterolemia
|
0.700 |
Biomarker
|
disease |
BEFREE |
We developed mice lacking lipin-1 in myeloid-derived cells and used adeno-associated viral vector 8 expressing the gain-of-function mutation of mouse proprotein convertase subtilisin/kexin type 9 (adeno-associated viral vector 8-proprotein convertase subtilisin/kexin type 9) to induce hypercholesterolemia and plaque formation.
|
29217509 |
2018 |
|
Hypercholesterolemia
|
0.700 |
Biomarker
|
disease |
BEFREE |
Inhibition of PCSK9 is emerging as a novel strategy for the treatment of hypercholesterolemia and data obtained from pre-clinical studies show that use of monoclonal antibodies, antisense oligonucleotides and short interfering RNA are effective in reducing LDL-C, clinical studies, accompanied by a better understanding of PCSK9 biology, are now necessary to address whether these new compounds will have a future in clinical practice.
|
21943799 |
2011 |
|
Hypercholesterolemia
|
0.700 |
Biomarker
|
disease |
BEFREE |
Three genes causative for FH (LDLR, APOB, and PCSK9) were sequenced in 636 patients with severe hypercholesterolaemia (mean age, 45 years; 300 males [47%], CAD diagnosis, 185 [29%]), and the presence of clinical FH signs (xanthoma and/or family history) were assessed.
|
28159968 |
2017 |
|
Hypercholesterolemia
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
PCSK9 gain of function mutations cause hypercholesterolaemia by a reduction of LDL receptor levels, while PCSK9 loss of function variants are associated with a reduction of LDL-C values and a decreased risk of coronary heart disease.
|
18708425 |
2008 |
|
Hypercholesterolemia
|
0.700 |
Biomarker
|
disease |
BEFREE |
Gain-of-function mutations of PCSK9 induce ADH and are very rare, but their identification is crucial in studying PCSK9's role in hypercholesterolemia, its detailed trafficking pathway and its impact on the LDLR.
|
22683120 |
2012 |
|
Hypercholesterolemia
|
0.700 |
Biomarker
|
disease |
BEFREE |
Currently, statins, Ezetimibe, Bile acid sequestrants and PCSK9 inhibitors are the main therapeutic agents for the treatment of hypercholesterolemia.
|
29578362 |
2018 |
|
Hypercholesterolemia
|
0.700 |
Biomarker
|
disease |
BEFREE |
Recently, biologic and genetic research proposed several approaches to inhibit or reduce PCSK9 to improve lipid profile and cardiovascular performance in patients with dyslipidemia, particularly hypercholesterolemia.
|
25444750 |
2015 |
|
Hypercholesterolemia
|
0.700 |
Biomarker
|
disease |
BEFREE |
PCSK9, through promoting lysosomal degradation of hepatic low-density lipoprotein (LDL) receptor, can decrease the clearance of plasma LDLs, leading to hypercholesterolaemia and consequent atherosclerotic plaque formation.
|
31236571 |
2019 |