|
Hypercholesterolemia
|
|
0.100 |
GeneticVariation
|
BEFREE |
Huh7 human hepatoma cells were transiently transfected to overexpress the gain-of-function D374Y PCSK9 mutation, which has been associated with severe hypercholesterolemia in humans.
|
31564372 |
2020 |
|
Hypercholesterolemia
|
|
0.100 |
GeneticVariation
|
BEFREE |
D374Y-PCSK9 transgenic pigs displayed reduced hepatic low-density lipoprotein (LDL) receptor levels, impaired LDL clearance, severe hypercholesterolemia, and spontaneous development of progressive atherosclerotic lesions that could be visualized by noninvasive imaging.
|
23283366 |
2013 |
|
Hypercholesterolemia
|
|
0.100 |
GeneticVariation
|
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 |
|
Hypercholesterolemia
|
|
0.100 |
GeneticVariation
|
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
|
|
0.100 |
GeneticVariation
|
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
|
|
0.100 |
GeneticVariation
|
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
|
|
0.100 |
GeneticVariation
|
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
|
|
0.100 |
GeneticVariation
|
BEFREE |
The objective of this study was to investigate possible mechanisms by which mutation D374Y in the PCSK9 gene causes hypercholesterolemia.
|
16777760 |
2006 |
|
Hypercholesterolemia
|
|
0.100 |
GeneticVariation
|
BEFREE |
Severe hypercholesterolemia in four British families with the D374Y mutation in the PCSK9 gene: long-term follow-up and treatment response.
|
16224054 |
2005 |
|
Hypercholesterolemia
|
|
0.100 |
GeneticVariation
|
BEFREE |
D374Y segregated with hypercholesterolemia in the two former families where family members were available for study.
|
15099351 |
2004 |
|
Atherosclerosis
|
|
0.020 |
GeneticVariation
|
BEFREE |
D374Y gain-of-function mutations in the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene cause severe autosomal dominant hypercholesterolemia and accelerates atherosclerosis in humans.
|
23283366 |
2013 |
|
Hyperlipoproteinemia Type IIa
|
|
0.020 |
GeneticVariation
|
BEFREE |
D374Y gain-of-function mutations in the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene cause severe autosomal dominant hypercholesterolemia and accelerates atherosclerosis in humans.
|
23283366 |
2013 |
|
Arteriosclerosis
|
|
0.020 |
GeneticVariation
|
BEFREE |
D374Y gain-of-function mutations in the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene cause severe autosomal dominant hypercholesterolemia and accelerates atherosclerosis in humans.
|
23283366 |
2013 |
|
Atherosclerosis
|
|
0.020 |
GeneticVariation
|
BEFREE |
To produce transgenic mice expressing the D374Y variant of the human proprotein convertase subtilisin/kexin type 9 (PCSK9) gene at physiological levels to investigate the mechanisms causing hypercholesterolemia and accelerated atherosclerosis.
|
20448210 |
2010 |
|
Arteriosclerosis
|
|
0.020 |
GeneticVariation
|
BEFREE |
To produce transgenic mice expressing the D374Y variant of the human proprotein convertase subtilisin/kexin type 9 (PCSK9) gene at physiological levels to investigate the mechanisms causing hypercholesterolemia and accelerated atherosclerosis.
|
20448210 |
2010 |
|
Hypercholesterolemia, Familial
|
|
0.020 |
GeneticVariation
|
BEFREE |
We measured plasma PCSK9 concentrations in healthy men with a PCSK9 (proprotein convertase subtilisin/kexin type 9) loss-of-function variant (p.R46L), in statin-treated patients with a clinical diagnosis of familial hypercholesterolemia (FH) and carrying a PCSK9 gain-of-function mutation (p.D374Y), and in statin-treated patients with FH due to different genetic causes.
|
19797716 |
2009 |
|
Hyperlipoproteinemia Type IIa
|
|
0.020 |
GeneticVariation
|
BEFREE |
We measured plasma PCSK9 concentrations in healthy men with a PCSK9 (proprotein convertase subtilisin/kexin type 9) loss-of-function variant (p.R46L), in statin-treated patients with a clinical diagnosis of familial hypercholesterolemia (FH) and carrying a PCSK9 gain-of-function mutation (p.D374Y), and in statin-treated patients with FH due to different genetic causes.
|
19797716 |
2009 |
|
Hypercholesterolemia, Familial
|
|
0.020 |
GeneticVariation
|
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 |
|
Cardiovascular Diseases
|
|
0.010 |
GeneticVariation
|
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 |
|
Hypocholesterolemia
|
|
0.010 |
GeneticVariation
|
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 |
|
Familial hypercholesterolemia - heterozygous
|
|
0.010 |
GeneticVariation
|
BEFREE |
Analysis of long-term (30 years) clinical history and response to treatment of 13 patients with the D374Y mutation of PCSK9 (PCSK9 patients) from 4 unrelated white British families compared with 36 white British patients with heterozygous familial hypercholesterolemia attributable to 3 specific mutations in the low-density lipoprotein (LDL) receptor gene (LDLR) known to cause severe phenotype.
|
16224054 |
2005 |