Yokoyama K, Tsakuda T, Saito H, Ubara Y, Katori H, et al
Is the polymorphism of the endothelial nitric oxide synthase (eNOS)
gene a predictor for progression of chronic renal diseases?
Am Soc Nephrol
J Am Soc Nephrol (abstract)
(Sep) 7:1326 1996
The rate of progression of chronic renal disease varies widely among
patients. While pharmacologic interventions have shown that ACE
inhibitors slow the progression of chronic renal failure, the explanation
for heterogenous rates of progression remain mysterious. One 'shotgun'
approach to this problem is to identify several candidate genes that might
contain subtle variations (allelic polymorphisms). DNA is isolated from
many well-characterized patients, and examined for subtle DNA
sequence variations. For progression of renal failure, one could envision
subtle alterations in vasoconstrictors, vasodilators, ion channels,
atherogenic factors, and growth factors and their associated receptors
(just to name a few possibilities).
This paper looks at two candidate genes:
the endothelial isoform of nitric oxide synthase, and angiotensin
converting enzyme. Endothelial nitric oxide synthase, the enzyme that
produces vasodilatory nitric oxide in blood vessels, is an attractive
candidate gene since NO has anti-atherogenic actions that could alter the
rate of progression. Recently, a polymorphism in the endothelial isoform
of NO synthase (eNOS) was identified which is associated with
coronary artery disease. ACE is an important candidate since ACE
inhibition slows progression of chronic renal failure.
This abstract
examined the incidence of polymorphisms for these genes in 58 non-diabetic
patients
with chronic renal failure on hemodialysis and 138 normal controls.
They found that the HD patients had a higher prevalence of the new 'b'
allele of eNOS (31% vs. 18% in controls), and the D allele of ACE (79%
vs. 53% in controls). The authors claim that the endothelial NOS gene
polymorphism is an important predictor for progression of non-diabetic
chronic renal failure.
Comment: I suspect that we will see a great deal more of this
type of study in the future. While the genetic analysis may be state of
the art, the conclusions must still be based upon the groups of patients
studied. Careful diagnosis and description of the patients are
necessary. This abstract used the wrong comparison group. They
should have measured the prevalence of the 'b' allele in patients who do
not progress, or who progress slowly.
(Robert A. Star, M.D., University of Texas Southwestern Medical
School, Dallas)
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Am Soc Nephrol
CRF by problem area :
Progression
H: Pathophysiology :
Endothelium, Nitric Oxide