|
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 |
Logistic regression analysis showed a trend of association between PCSK9 E670G and hypercholesterolemia after adjustment for covariates (P = .059).
|
24793346 |
2015 |
|
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 |
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 |
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 |
GeneticVariation
|
disease |
BEFREE |
Gain-of-function mutations within proprotein convertase subtilisin kexin type 9 (PCSK9) are linked to familial autosomal dominant hypercholesterolaemia, a disease characterized by elevated plasma concentrations of cholesterol associated with low-density lipoproteins (LDLs).
|
18672372 |
2008 |
|
Hypercholesterolemia
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
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 |
BEFREE |
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 |
GeneticVariation
|
disease |
BEFREE |
Gain-of-function and loss-of-function mutations within PCSK9 gene lead to hypercholesterolemia or hypocholesterolemia respectively.
|
21040917 |
2010 |
|
Hypercholesterolemia
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Several gain-of-function and loss-of-function mutations in the PCSK9 gene have been identified and linked to hypercholesterolemia and hypocholesterolemia, respectively.
|
21619378 |
2011 |
|
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 |
GeneticVariation
|
disease |
BEFREE |
Mutations of PCSK9 are associated either with hypercholesterolemia or with hypocholesterolemia.
|
17495605 |
2007 |
|
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 |
PheWAS revealed a significantly reduced risk of hypercholesterolemia (odds ratio [OR] 0.68, p = 7.6 × 10<sup>-4</sup>) in association with a known loss-of-function variant in PCSK9, R46L.
|
29185237 |
2018 |
|
Hypercholesterolemia
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
PCSK9 mutant proteins associated with hypercholesterolemia (S127R and D374Y) are more potent in decreasing LDL uptake than is wild-type PCSK9.
|
18354137 |
2008 |
|
Hypercholesterolemia
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Patients with mutations in the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene have hypercholesterolemia and are at high risk of adverse cardiovascular events.
|
25341796 |
2015 |
|
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 |
GeneticVariation
|
disease |
BEFREE |
Mutations in the PCSK9 gene have been associated with both hypocholesterolemia and hypercholesterolemia through 'loss-of-function' and 'gain-of-function' mechanisms, respectively.
|
16571601 |
2006 |
|
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 |
The objective of this study was to investigate possible mechanisms by which mutation D374Y in the PCSK9 gene causes hypercholesterolemia.
|
16777760 |
2006 |
|
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 |
GeneticVariation
|
disease |
BEFREE |
Patients with heterozygous familial hypercholesterolemia or severe hypercholesterolemia with untreated LDL-C levels ≥220 mg/dL also should experience reasonable or high value from PCSK9 mAbs when LDL-C is ≥100 mg/dL for primary prevention and ≥70 mg/dL for secondary prevention.
|
31281070 |
2019 |
|
Hypercholesterolemia
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Gain-of-function mutations of the proprotein convertase subtilisin/kexin type 9 (PCSK9) are associated with hypercholesterolemia and increased risk of cardiovascular events.
|
23973703 |
2013 |
|
Hypercholesterolemia
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Polymorphisms in the proprotein convertase subtilisin/kexin type 9 (<i>PCSK9</i>) gene are associated with severe hypercholesterolemia and stroke.
|
28966647 |
2017 |
|
Hypercholesterolemia
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
The expression of human D374Y PCSK9 at physiological levels produced a phenotype that closely matched that found in heterozygous D374Y patients and suggested that reduced low-density lipoprotein receptor activity is not the sole cause of their hypercholesterolemia.
|
20448210 |
2010 |