Clinical Epigenetics,
Год журнала:
2021,
Номер
13(1)
Опубликована: Май 1, 2021
A
subset
of
individuals
with
type
1
diabetes
mellitus
(T1DM)
are
predisposed
to
developing
diabetic
kidney
disease
(DKD),
the
most
common
cause
globally
end-stage
(ESKD).
Emerging
evidence
suggests
epigenetic
changes
in
DNA
methylation
may
have
a
causal
role
both
T1DM
and
DKD.
The
aim
this
exploratory
investigation
was
assess
differences
blood-derived
patterns
between
T1DM-ESKD
long-duration
but
no
upon
repeated
testing
identify
potential
blood-based
biomarkers.
Blood-derived
from
(107
cases,
253
controls
14
experimental
controls)
were
bisulphite
treated
before
groups
generated
analysed
using
Illumina's
Infinium
MethylationEPIC
BeadChip
arrays
(n
=
862,927
sites).
Differentially
methylated
CpG
sites
(dmCpGs)
identified
(false
discovery
rate
adjusted
p
≤
×
10-8
fold
change
±
2)
by
comparing
levels
ESKD
cases
at
single
site
resolution.
Gene
annotation
functionality
investigated
enrich
rank
regions
associated
T1DM.Top-ranked
genes
within
which
several
dmCpGs
located
supported
functional
data
look-ups
other
cohorts
include:
AFF3,
ARID5B,
CUX1,
ELMO1,
FKBP5,
HDAC4,
ITGAL,
LY9,
PIM1,
RUNX3,
SEPTIN9
UPF3A.
Top-ranked
enrichment
pathways
included
cancer,
TGF-β
signalling
Th17
cell
differentiation.Epigenetic
alterations
provide
dynamic
link
an
individual's
genetic
background
their
environmental
exposures.
This
robust
evaluation
carefully
phenotyped
has
biomarkers
ESKD,
revealing
implicated
key
T1DM.
Journal of Clinical Investigation,
Год журнала:
2023,
Номер
133(4)
Опубликована: Фев. 14, 2023
Kidney
disease
is
a
major
driver
of
mortality
among
patients
with
diabetes
and
diabetic
kidney
(DKD)
responsible
for
close
to
half
all
chronic
cases.
DKD
usually
develops
in
genetically
susceptible
individual
as
result
poor
metabolic
(glycemic)
control.
Molecular
genetic
studies
indicate
the
key
role
podocytes
endothelial
cells
driving
albuminuria
early
diabetes.
Proximal
tubule
changes
show
strong
association
glomerular
filtration
rate.
Hyperglycemia
represents
cellular
stress
by
altering
metabolism
imposing
an
excess
workload
requiring
energy
oxygen
proximal
cells.
Changes
induce
adaptive
hypertrophy
reorganization
actin
cytoskeleton.
Later,
mitochondrial
defects
contribute
increased
oxidative
activation
inflammatory
pathways,
causing
progressive
function
decline
fibrosis.
Blockade
renin-angiotensin
system
or
sodium-glucose
cotransporter
associated
protection
slowing
decline.
Newly
identified
molecular
pathways
could
provide
basis
development
much-needed
novel
therapeutics.
Kidney International,
Год журнала:
2022,
Номер
101(6), С. 1126 - 1141
Опубликована: Апрель 21, 2022
Numerous
genes
for
monogenic
kidney
diseases
with
classical
patterns
of
inheritance,
as
well
complex
that
manifest
in
combination
environmental
factors,
have
been
discovered.
Genetic
findings
are
increasingly
used
to
inform
clinical
management
nephropathies,
and
led
improved
diagnostics,
disease
surveillance,
choice
therapy,
family
counseling.
All
these
steps
rely
on
accurate
interpretation
genetic
data,
which
can
be
outpaced
by
current
rates
data
collection.
In
March
2021,
Kidney
Diseases:
Improving
Global
Outcomes
(KDIGO)
held
a
Controversies
Conference
"Genetics
Chronic
Disease
(CKD)"
review
the
state
understanding
(polygenic)
diseases,
processes
applying
medicine,
use
genomics
defining
stratifying
CKD.
Given
important
contribution
variants
CKD,
practitioners
CKD
patients
advised
"think
genetic,"
specifically
involves
obtaining
history,
collecting
detailed
information
age
onset,
performing
examination
extrarenal
symptoms,
considering
testing.
To
improve
genetics
nephrology,
meeting
participants
developing
an
advanced
training
or
subspecialty
track
nephrologists,
crafting
guidelines
testing
treatment,
educating
patients,
students,
practitioners.
Key
areas
future
research,
including
genome
variation,
electronic
phenotyping,
global
representation,
kidney-specific
molecular
polygenic
scores,
translational
epidemiology,
open
resources,
were
also
identified.
Cell Metabolism,
Год журнала:
2023,
Номер
35(4), С. 695 - 710.e6
Опубликована: Март 23, 2023
Associations
between
human
genetic
variation
and
clinical
phenotypes
have
become
a
foundation
of
biomedical
research.
Most
repositories
these
data
seek
to
be
disease-agnostic
therefore
lack
disease-focused
views.
The
Type
2
Diabetes
Knowledge
Portal
(T2DKP)
is
public
resource
datasets
genomic
annotations
dedicated
type
diabetes
(T2D)
related
traits.
Here,
we
make
the
T2DKP
more
accessible
prospective
users
useful
existing
users.
First,
evaluate
T2DKP's
comprehensiveness
by
comparing
its
with
those
other
repositories.
Second,
describe
how
researchers
unfamiliar
can
begin
using
correctly
interpreting
them
via
T2DKP.
Third,
extend
their
current
workflows
use
full
suite
tools
offered
We
finally
discuss
lessons
toward
goal
democratizing
access
complex
disease
results.
Endocrine Reviews,
Год журнала:
2023,
Номер
45(2), С. 227 - 252
Опубликована: Авг. 25, 2023
Chronic
complications
of
diabetes
are
due
to
myriad
disorders
numerous
metabolic
pathways
that
responsible
for
most
the
morbidity
and
mortality
associated
with
disease.
Traditionally,
divided
into
those
microvascular
macrovascular
origin.
We
suggest
revising
this
antiquated
classification
vascular,
parenchymal,
hybrid
(both
vascular
parenchymal)
tissue
origin,
since
profile
ranges
from
involving
only
tissues
mostly
parenchymal
organs.
A
major
paradigm
shift
has
occurred
in
recent
years
regarding
pathogenesis
complications,
which
focus
shifted
studies
on
risks
interplay
between
risk
protective
factors.
While
factors
clearly
important
development
chronic
diabetes,
have
established
equally
significant
modulating
severity
complications.
These
responses
may
help
explain
differential
even
lack
pathologies,
some
tissues.
Nevertheless,
despite
growing
number
field,
comprehensive
reviews
their
mechanisms
action
not
available.
This
review
thus
focused
clinical,
biochemical,
molecular
support
idea
endogenous
factors,
roles
initiation
progression
diabetes.
In
addition,
also
aimed
identify
main
needs
field
future
studies.