Pharmaceutics,
Год журнала:
2023,
Номер
15(7), С. 1995 - 1995
Опубликована: Июль 20, 2023
Diabetic
kidney
disease
(DKD)
is
a
severe
and
common
complication
affects
quarter
of
patients
with
type
2
diabetes
mellitus
(T2DM).
Oxidative
stress
inflammation
related
to
hyperglycemia
are
interlinked
contribute
the
occurrence
DKD.
It
was
shown
that
sodium–glucose
cotransporter-2
(SGLT2)
inhibitors,
novel
yet
already
widely
used
therapy,
may
prevent
development
DKD
alter
its
natural
progression.
SGLT2
inhibitors
induce
systemic
glomerular
hemodynamic
changes,
provide
metabolic
advantages,
reduce
inflammatory
oxidative
pathways.
In
T2DM
patients,
regardless
cardiovascular
diseases,
albuminuria,
progression
DKD,
doubling
serum
creatinine
levels,
thus
lowering
need
for
replacement
therapy
by
over
40%.
The
molecular
mechanisms
behind
these
beneficial
effects
extend
beyond
their
glucose-lowering
effects.
emerging
studies
trying
explain
at
genetic,
epigenetic,
transcriptomic,
proteomic
levels.
Nature,
Год журнала:
2023,
Номер
618(7966), С. 774 - 781
Опубликована: Май 17, 2023
Abstract
Polygenic
scores
(PGSs)
have
limited
portability
across
different
groupings
of
individuals
(for
example,
by
genetic
ancestries
and/or
social
determinants
health),
preventing
their
equitable
use
1–3
.
PGS
has
typically
been
assessed
using
a
single
aggregate
population-level
statistic
R
2
)
4
,
ignoring
inter-individual
variation
within
the
population.
Here,
large
and
diverse
Los
Angeles
biobank
5
(ATLAS,
n
=
36,778)
along
with
UK
Biobank
6
(UKBB,
487,409),
we
show
that
accuracy
decreases
individual-to-individual
continuum
7
in
all
considered
populations,
even
traditionally
labelled
‘homogeneous’
ancestries.
The
decreasing
trend
is
well
captured
continuous
measure
distance
(GD)
from
training
data:
Pearson
correlation
−0.95
between
GD
averaged
84
traits.
When
applying
models
trained
on
as
white
British
UKBB
to
European
ATLAS,
furthest
decile
14%
lower
relative
closest
decile;
notably,
Hispanic
Latino
American
similar
performance
significantly
correlated
estimates
themselves
for
82
traits,
further
emphasizing
importance
incorporating
interpretation.
Our
results
highlight
need
move
away
discrete
ancestry
clusters
towards
when
considering
PGSs.
Arteriosclerosis Thrombosis and Vascular Biology,
Год журнала:
2022,
Номер
43(1), С. 15 - 29
Опубликована: Ноя. 22, 2022
Cardiovascular
disease
is
the
most
common
cause
of
death
worldwide,
especially
beyond
age
65
years,
with
vast
majority
morbidity
and
mortality
due
to
myocardial
infarction
stroke.
Vascular
pathology
stems
from
a
combination
genetic
risk,
environmental
factors,
biologic
changes
associated
aging.
The
pathogenesis
underlying
development
vascular
aging,
calcification
in
particular,
still
not
fully
understood.
Accumulating
data
suggests
that
likely
compounded
by
epigenetic
modifications,
including
diabetes
chronic
kidney
disease,
plasticity
smooth
muscle
cells
acquire
an
osteogenic
phenotype
are
major
determinants
age-associated
calcification.
Understanding
molecular
mechanisms
modifiable
risk
factors
regulating
may
inspire
strategies
promote
healthy
This
article
summarizes
current
knowledge
concepts
emphasis
on
Abstract
Polygenic
scores
(PGS)
can
be
used
for
risk
stratification
by
quantifying
individuals’
genetic
predisposition
to
disease,
and
many
potentially
clinically
useful
applications
have
been
proposed.
Here,
we
review
the
latest
potential
benefits
of
PGS
in
clinic
challenges
implementation.
could
augment
through
combined
use
with
traditional
factors
(demographics,
disease-specific
factors,
family
history,
etc.),
support
diagnostic
pathways,
predict
groups
therapeutic
benefits,
increase
efficiency
clinical
trials.
However,
there
exist
maximizing
utility
PGS,
including
FAIR
(Findable,
Accessible,
Interoperable,
Reusable)
standardized
sharing
genomic
data
needed
develop
recalculate
equitable
performance
across
populations
ancestries,
generation
robust
reproducible
calculations,
responsible
communication
interpretation
results.
We
outline
how
these
may
overcome
analytically
more
diverse
as
well
highlight
sustained
community
efforts
achieve
equitable,
impactful,
healthcare.
