Abstract
Background
High
LDL-cholesterol
(LDL-C)
is
a
well-known
risk
factor
for
coronary
artery
disease
(CAD).
PCSK9,
HMGCR,
NPC1L1,
ACLY,
and
LDLR
gene
have
been
reported
as
lipid
lowering
drug
genes
related
to
LDL-C
lowering.
However
relevant
Asian
studies
were
rare.
Methods
We
examined
the
causality
between
LDL-c
target
CAD
using
Korean
Japanese
data
two
sample
Mendelian
Randomization
(MR)
method.
conducted
two-sample
MR
analysis
of
(7
Single-nucleotide
polymorphisms
(SNP)
in
PCSK9,
6
SNPs
HMGCR,
5
NPC1L1,
9
ACLY,
3
LDLR)
CAD.
used
summary
statistics
from
Genome
Epidemiology
Study
(KOGES)
data,
Biobank
Japan
(BBJ)
data.
Results
For
every
10
mg/dl
decrease
determined
by
four
significant
PCSK9
gene,
decreased
approximately
20%
(OR
=
0.80,
95%
CI:
0.75–0.86).
The
10%
due
six
HMGCR
0.90,
0.86–0.94).
Due
LDLR,
26%
0.74,
0.66–0.82).
combined
effect
on
showed
largest
size
PCSK9
LDLR
reduced
induced
these
together
was
OR
0.78
(95%CI,
0.74–0.83).
Finally,
all
three
(PCSK9,
LDLR)
0.85
0.79–0.91)
(Fig.
3D).
Conclusion
reduction
estimated
significantly
found
potential
proxy
research
design
clinical
trials
drugs.
Research Square (Research Square),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Nov. 6, 2024
Abstract
Introduction:
Celiac
disease
(CeD)
is
an
autoimmune
condition
characterized
by
a
reversible
inflammatory
reaction
in
the
mucous
membrane
of
small
intestine.
Nevertheless,
there
limited
availability
efficient
control
approaches.
Prior
research
has
demonstrated
that
pharmacological
targets
supported
genetic
evidence
can
greatly
enhance
efficacy
drug
development.
Hence,
study
aims
to
integrate
transcriptomic
and
proteomic
information
identify
candidate
for
CeD.
Methods
The
employed
proteome-wide
Mendelian
randomization
(MR)
analysis
circulating
plasma
proteins
investigate
their
causal
association
with
CeD
were
further
assessed
employing
colocalization
analysis,
transcriptome-wide
summary-data-based
(SMR)
multimarker
genomic
annotation
(MAGMA)
gene-based
bulk
RNAseq-based
differential
expression
analysis.
For
identified,
extended
Phenome-wide
studies
(PheWAS)
conducted
assess
side-effect
profiles,
while
DGIdb
database
provided
on
approved
or
investigated
drugs
targets.
Results
Systematic
MR
identified
22
Among
analyzed,
BTN2A1
passed
all
subsequent
verification
analyses.
Additionally,
three
proteins,
including
CatH,
IL-18R1,
PTPRC,
majority
other
18
also
(Trehalase,
CD226,
SH2B3,
ICOSLG,
ULK3,
Park7,
ALDH2,
RABEP1,
TNFRSF9,
COL11A2,
GNPDA1,
IL-1RL1,
B3galt6,
TNFSF11,
CCL21,
BTN3A3,
OLFM2
Colipase).
Conclusions
combination
human
information,
several
analytical
methods.
As
result,
divided
into
four
tiers,
as
prospective
therapeutic
Journal of Inflammation Research,
Journal Year:
2024,
Volume and Issue:
Volume 17, P. 8569 - 8587
Published: Nov. 1, 2024
Intracranial
aneurysms
(IA)
frequently
cause
subarachnoid
hemorrhage
(SAH)
and
have
poor
prognosis.
However,
the
molecular
mechanisms
diagnostic
biomarkers
associated
with
IA
ruptured
(rIA)
remain
poorly
understood.
