RAS and ecNOS Gene Polymorphisms in Dialysis Patients: Influence on Survival
Journal Name:
- Türk Nefroloji, Diyaliz ve Transplantasyon Dergisi
Keywords (Original Language):
Abstract (2. Language):
Survival for patients with end-stage renal disease is influenced
by many environmental and genetic factors. In this study, we aimed
to define influence of angiotensin-converting enzyme (ACE), angiotensinogen
(AGT), and angiotensin II type 1 and 2 (ATR1 and ATR2)
receptors in the renin-angiotensin system (RAS), as well as endothelial
constitutive nitric oxide synthase (ecNOS) gene polymorphisms
on patient survival, in a population of Turkish patients with end-stage
renal disease. One hundred and sixty-seven patients followed either
by hemodialysis (n: 91) or continuous ambulatory peritoneal dialysis
(n: 76) were included in this study. Genotyping was performed for the
insertion/deletion of ACE (I/D), AGT (M—T, 235), ATR1 (A—C, 1166),
ATR2 (A—G, 1223), and ecNOS (b—a, intron 4) gene polymorphisms.
Retrospective data for the prior 12 months, including clinical and demographic
data were collected and analyzed. Polymorphism percentages
were ATR1:AA/AC/CC, 64%, 34.7%, and 1.3%; ATR2: AA/AC/CC,
17.7%, 32%, and 50.3%; AGT:TT/TC/CC, 32%, 66%, and 2%;
ACE:DD/ID/II, 51.4%, 38.5%, and 10.1%; and ecNOS:aa/ab/bb, 7.6%,
24.3%, and 68.1%, respectively. Our analyzes revealed that; in
patients who were recieving hemodialysis for more than 5 years
(n:85) prevalence of the bb variant of ecNOS gene was higher
(73.4% vs 63.9%, P < 0.05) than the ones with shorter dialysis duration
(n:82). There were no statistically significant differences between
groups in terms of RAS gene polymorphisms. Further analysis revealed
that bb variant was also more prevalent in patients with longterm
survival with known adverse RAS variants. We conclude therefore,
that the high prevalence of the bb variant of the ecNOS gene
polymorphism seen in Turkish patients with end-stage renal disease
undergoing dialysis possibly balances increased RAS activity and influences
long-term survival.
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Abstract (Original Language):
Çalışmamızda, merkezimizde diyaliz tedavisi gören hasta popülasyonunda,
renin-anjiyotensin sisteminden (RAS) anjiyotensin
değiştirici enzim (ADE), anjiyotensinojen (AGT), anjiyotensin II tip 1
(ATR1) ve anjiyotensin II tip 2 (ATR2) reseptörleri ve endotelyal nitrik
oksit sentaz enzimi (ecNOS) gen poliformizmlerinin frekansını
ve sağkalım üzerine olası etkilerini tanımlamayı amaçladık. Çalışmaya
hemodiyaliz (n: 91) ya da sürekli ayaktan periton diyalizi
(n: 76) tedavisi almakta olan toplam 167 hasta dahil edildi. Tüm
hastalarda ADE (I/D), AGT (M—T, 235), ATR1 (A—C, 1166), ATR2
(A—C, 1223) ve ecNOS (b—a, intron 4) gen polimorfizmlerinin insersiyon/
delesyon varyant frekanslarını belirlemek amacıyla genotiplendirme
yapıldı. Klinik, demografik ve laboratuvar veriler retrospektif
olarak toplandı. Polimorfizm yüzdeleri sırasıyla;
ATR1:AA/AC/CC %64, %34.7 ve %1.3; ATR2:AA/AC/CC %7.7,%32 ve
%50.3; AGT:TT/TM/MM %32,%66 ve %2; ADE:DD/ID/II %51.4,%38.5
ve %10.1 ve ecNOS: aa/ab/bb %7.6,%24.3 ve %68.1 idi. ecNOS bb
varyant frekansı 5 yıldan daha uzun süredir diyaliz tedavisi alan
hastalarda anlamlı olarak daha yüksekti (73.4%, 63.9%, P < 0.05).
Artmış RAS aktivitesi ile ilişkili olduğu bilinen RAS varyantlarına
sahip olan ancak sağkalım süresi uzun olan hastalarda da bb var¬
yant sıklığı göreli olarak daha fazlaydı. Bu bulgulara dayanarak hasta
popülasyonumuzda görülen artmış bb varyant frekansının muhtemelen
artmış RAS aktivitesini dengeleyerek uzun süreli sağkalım
üzerinde olumlu etkilerinin olabileceği sonucuna vardık.
FULL TEXT (PDF):
- 4
177-182