|
Hypercholesterolemia
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
We sequenced the LDLR 3' and 5' untranslated regions (UTR) and the PCSK9 5' UTR of 102 participants with moderate hypercholesterolemia in trial NCT01562080.
|
27015087 |
2016 |
|
Hypercholesterolemia
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
We propose the following classification: familial hypercholesterolemia syndrome integrated by (1) heterozygous familial hypercholesterolemia: patients with clinically definite FH and a functional mutation in one allele of the LDLR, ApoB:100, and PCSK9 genes; (2) homozygous familial hypercholesterolemia: mutations affect both alleles; (3) polygenic familial hypercholesterolemia: patients with clinically definite FH but no mutations associated with FH are found (to be distinguished from non-familial, multifactorial hypercholesterolemia); (4) familial hypercholesterolemia combined with hypertriglyceridemia: a subgroup of familial combined hyperlipidaemia patients fulfilling clinically definite FH with associated hypertriglyceridemia.
|
31238171 |
2019 |
|
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 |
GeneticVariation
|
disease |
BEFREE |
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 |
GeneticVariation
|
disease |
BEFREE |
We found 2 true homozygotes for PCSK9 E32K and 3 double heterozygotes for PCSK9 E32K and LDLR mutations associated with autosomal dominant hypercholesterolaemia.
|
20006333 |
2010 |
|
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 |
We conducted a comprehensive search of electronic databases, up to December 1, 2018, for all RCTs comparing PCSK9 inhibition to placebo or ezetimibe in patients with hypercholesterolemia or coronary artery disease receiving maximally tolerated statin for primary or secondary prevention of mortality and cardiovascular outcomes.
|
31679643 |
2019 |
|
Hypercholesterolemia
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
We also highlight the spectrum of hypercholesterolemia or hypobetalipoproteinemia phenotypes that are already associated with mutations in PCSK9.
|
19191301 |
2009 |
|
Hypercholesterolemia
|
0.700 |
Biomarker
|
disease |
BEFREE |
Very recent treatment strategies include the PCSK9 inhibitors for hypercholesterolaemia and the SGLT2 inhibitors for reduction of cardiovascular events in patients with diabetes mellitus and increased cardiovascular risk.
|
30338502 |
2019 |
|
Hypercholesterolemia
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Using this cell-based assay of PCSK9 activity, we found that the relative potencies of several PCSK9 missense mutants (S127R and D374Y, associated with hypercholesterolemia, and R46L, associated with hypocholesterolemia) correlate with LDL cholesterol levels in humans carrying such mutations.
|
17493938 |
2007 |
|
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 |
BEFREE |
To gain insight into recruitment of different plaque SMCs, we mapped their clonal architecture in aggregation chimeras of eGFP+Apoe-/- and Apoe-/- mouse embryos and in mice with a mosaic expression of fluorescent proteins in medial SMCs that were rendered atherosclerotic by PCSK9-induced hypercholesterolemia.
|
28978793 |
2017 |
|
Hypercholesterolemia
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
To block secreted PCSK9 activity, LDLR (H306Y) subfragments were added to the medium of HepG2 cells stably overexpressing wild-type PCSK9 or gain-of-function PCSK9 mutants associated with hypercholesterolemia (D374Y or S127R).
|
19224862 |
2009 |
|
Hypercholesterolemia
|
0.700 |
Biomarker
|
disease |
BEFREE |
To assess the lipid-lowering efficacy and safety of alirocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, in people with hypercholesterolaemia and prediabetes at baseline vs people with normoglycaemia at baseline in a pooled analysis of 10 ODYSSEY phase III trials.
|
28799203 |
2018 |
|
Hypercholesterolemia
|
0.700 |
Biomarker
|
disease |
BEFREE |
Thus, PCSK9 inhibitors may also be recommended as promisingly first-line lipid-lowering treatment for patients with hypercholesterolemia, especially for these with statins intolerance or resistance.
|
30732185 |
2019 |
|
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 |
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 |
This led to FDA removal of the requirement to monitor liver function tests in patients on statin therapy.The combination of statins with other compounds such as ezetimibe or PCSK9 inhibitors has shown some additional benefits in the treatment of hypercholesterolemia.
|
31773344 |
2019 |
|
Hypercholesterolemia
|
0.700 |
AlteredExpression
|
disease |
BEFREE |
This decrease is related to low cholesterol levels in Pcsk9(-/-) mice, as the protection was lost after normalizing Pcsk9(-/-) cholesterol levels by a 2-week high cholesterol diet.
|
23308045 |
2012 |
|
Hypercholesterolemia
|
0.700 |
Biomarker
|
disease |
BEFREE |
This challenging work in the genetics of hypercholesterolemia paved the way for a plethora of studies around the world allowing the characterization of PCSK9, its expression, its impact on reducing the abundance of LDL receptor, and the identification of loss-of-function mutations in hypocholesterolemia.
|
25052769 |
2014 |
|
Hypercholesterolemia
|
0.700 |
Biomarker
|
disease |
BEFREE |
Therefore, PCSK9 inhibitors become novel therapeutic approaches in the treatment of hypercholesterolemia.
|
29692249 |
2019 |
|
Hypercholesterolemia
|
0.700 |
AlteredExpression
|
disease |
BEFREE |
Therefore development of new LDL-C lowering medications that either do not increase circulating PCSK9 levels or work through inhibition of PCSK9 expression and protease activity is a highly desirable approach to overcome hypercholesterolemia.
|
22311433 |
2012 |
|
Hypercholesterolemia
|
0.700 |
Biomarker
|
disease |
BEFREE |
There is a wealth of evidence indicating that inhibition of PCSK9 is a highly desirable approach to combat hypercholesterolemia, with several agents in preclinical and clinical development.
|
21204732 |
2011 |
|
Hypercholesterolemia
|
0.700 |
Biomarker
|
disease |
BEFREE |
The use of therapeutic monoclonal antibodies to target proprotein convertase subtilisin/kexin type 9 (PCSK9) represents a novel approach to the management of hypercholesteremia and prevention of atherosclerotic cardiovascular disease.
|
31246589 |
2019 |
|
Hypercholesterolemia
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
The two PCSK9 mutations are novel and were not found in 110 controls and 80 patients with co-dominant hypercholesterolemia.
|
16183066 |
2006 |