I. Gomez-Farices. MA, McClellan .... H, Passa. P, Froguel. P, Ruiz J: Paraoxonase polymorphism. Met-Leu. 54 is associated ... L, Leroux-Robert. C: Paraoxonase.
J Am
Decrease of Serum Renal Failure
Paraoxonase
THIERRY F. DANTOINE,* LOUIS MERLE,t PIERRE CLAUDE LEROUXROBERT* *Nephrology
Unit
and
Activity
9: 2082-2088,
1998
in Chronic
JEAN DEBORD,t JEAN-PIERRE MARQUET,t GERARD LACHATRE,t
Department
Nephrol
Soc
of Pharmacology-Toxicology,
CHARMES,* and
Dupuytren
University
Hospital,
Limoges,
France.
Paraoxonase compounds.
Abstract.
phosphate and
could
protect
possible
familial
is associated
paraoxonase
Paraoxonase
with
the
main
cause
infarction,
death
three
was
synthetic
4-nitrophenyl
in
acetate)
in
305
patients
Cardiovascular
disease
is the main
failure
(CRF)
patients
(accounting
cases;
references
1 and
tion
is five times
greater
than
in the general
(3).
No clear
and
contribute
abnormalities, atherosclerosis
dyslipidemias studies
CRF against
have
shown
patients,
a higher might
processes the arterial
leading wall:
toward
of LDL
cells,
and
growth
and
factors)
(10,1
acid
against
esters
human
serum
and
shown
several
of Nephrology,
a blue ribbon. Correspondence Limoges,
to
2 Avenue
New Dr.
Orleans,
Jean-Pierre
Martin
Luther
LA,
November
Charmes, King,
3-6,
reduced
the
to
teins
against
LDL
production
gous
1), several
(1 7, 1 8).
Service
87042
Limoges
a
Copyright
of the ©
American 1998
by the
Society American
and
received
Nephrologie, Cedex,
France.
Chu
[high
Society
of Nephrology
with
activity])
age
studies
have
been
is related
variation
but
lipid
to induce
monorole
of
this
mellitus, that
in high heterozy-
myocardial
showed
hypoth-
noticed
infarction paraoxonase
(19). a triphasic
paraoxon: AB
defined
to a single
distribution
Three
[intermediate
(20-22).
two
amino
polymorphism
paraoxonase
acid
of serum
phenotypes
Genetic
studies
isozymes
(glutarnine
of the paraoxonase
and
and BB
activity],
have whose
or arginine gene
shown to affect the concentration its specific activity (24-26). Recently,
it has been
not
support
or
with
A second
54 is known;
of paraoxonase,
been
LDL significantly
was
diabetes we
toward activity],
difference
linking has
a protective
activity
with
[low
that
LDL Thus,
Other
display
activity
associated
position
of Nephrology
oxidized
study,
populations (AA
decreased paraoxonase
(16).
patients
previous
decreased
genotypes
It
hypercholesterolemia,
In
191) (23,24).
1046-6673/0901 1-2082$03.00/0 Journal
de
of the American
atherosclerosis:
a decreased
risk
familial
4-nitrophenyl
atherosclerosis has been suggested, as of the protective role of HDL lipopro-
that
cardiovascular
and
emerged
purified
oxidation.
showing
its procom-
has
paraoxonase
that
for
metabolite of parathion: several aromatic carboxacetate
to
to
paraoxonase/
known
of organophosphorus
evidence
of mildly
of
first
es-
seems
enzyme
phenyl
interactions
paraoxonase against well as an explanation by
as
and
ability
paraoxonase 1996,
some
aging,
transplantation
was
recently, purified
(15)
Caucasian
Society
with
[P < 0.05],
failure
vascular
HDL-linked
paraoxonase
cyte-endothelial
esis
Renal
the toxic to hydrolyze
(such
in vitro
that
activity
Received August 12, 1997. Accepted May 4, 1998. These data were presented in part at the 29th Annual Meeting
sub-
4-nitrophenyl
in patients renal
of premature
the toxicity
More
peroxidation in
the
hydrolyzing and its ability
trans-
a number
immunogenicity,
(by
(14).
to the formation of atherosclerotic plaques in enhancement of macrophage uptake, cytotox-
cytokines,
pounds paraoxon) acetate)
seems
promoting
studied
activity
ylic
lipoproteins
of atherosclerosis
factor
( 12, 13). Paraoxonase
arylesterase
tective
(7-9).
LDL
be an essential
have
of
to oxidation
of
with
lower
Patients
control
hemodialysis [P < b01, chronic peritoneab dialysis l0]) than in control subjects. In transplant patients, paraoxonase activity was not found to be different from that in control subjects. The decrease of paraoxonase activity and thus the reduction of its antiatherogenic properties in renal failure
groups
of mortality,
protection
hypothesis (oxidized
endothelial
of oxysterols,
the
renal
was
(chronic
renal
factors, melbitus,
(6). Recently,
susceptibility
be impaired
established
cause
observed
that
the oxidation
(4,5). After
a major
frequently
suggesting
oxidation
Because
remains
also
are
be currently
icity
may
activity
insufficiency
when dialysis is used. paraoxonase activity.
of this
Several diabetes
patients.
Especially
peciably restore
infarctherapy
explanation
transplant of aged-matched
195).
=
paraoxonase
renal
groups
with
50%
relative risk of myocardial in patients on renal replacement has been found. of hypertension,
plantation,
in chronic
approximately
“accelerated” atherosclerosis including increased prevalence lipid
failure,
treated
of death
for
132
two
number
of renal
could
disease,
renal
22 patients
cause
usand
kidney
chronic
and with
[P