You are here

Home » Content

Diyaliz Hastalarında RAS ve ecNOS Gen Polimorfizmleri: Sağkalım Üzerine Olası Etkileri

RAS and ecNOS Gene Polymorphisms in Dialysis Patients: Influence on Survival

Journal Name:

  • Türk Nefroloji, Diyaliz ve Transplantasyon Dergisi

Publication Year:

  • 2005

Key Words:

Keywords (Original Language):

Author NameUniversity of Author
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.
Bookmark/Search this post with
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): 
PDF icon pdf_tndt_545.pdf
  • 4
177-182
  • Turkish

REFERENCES

References: 

1. Asakimori Y, Yorioka N, Yamamoto I, Okumoto S, Doi S, Hirai T, et al. Endothelial nitric oxide synthase intron 4 polymorphism influences the progression of renal disease. Nephron 2001;89(2): 219-23.
2. Miyamoto Y, Saito Y, Kajiyama N, Yoshimura M, Shimasaki Y, Na-kayama M, et al. Endothelial nitric oxide synthase gene is positi¬vely associated with essential hypertension. Hypertension 1998;
32(1):3-8.
3. Sakka Y, Babazono T, Sato A, Ujihara N, Iwamoto Y, et al. ACE gene polymorphism, left ventricular geometry, and mortality in diabetic patients with end-stage renal disease. Diabetes Res Clin Pract 2004;64(1):4l-9.
4. Takami S, Katsuya T, Rakugi H, Sato N, Nakata Y, Kamitani A, et al. Angiotensin II Type 1 receptor gene polymorphism is associ¬ated with increase of left ventricular mass but not with hyperten¬sion. Am J Hypertens 1998;11(3 Pt 1):316-21.
5. Lovati E, Richard A, Frey BM, Frey FJ, Ferrari P. Genetic polymorp¬hisms of the renin-angiotensin-aldosterone system in end-stage re¬nal disease. Kidney Int 2001; 60(1):46-54.
6. Wong TY, Szeto CC, Chow KM, Chan JC, Li PK. Contribution of gene polymorphism in the renin-angiotensin system to macroan-giopathy in patients with diabetic nephropathy. Am J Kidney Dis 2001;38(1):9-17.
7. Rigat B, Hubert C, Alhenc-Gelas F, et al. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene acco¬unting for half the variance of serum enzyme levels. J Clin Invest 1990;86(4):1343-6.
8. Cambien F, Poirier O, Lecerf L, et al. Deletion polymorphism in the gene for angiotensin-converting enzyme gene is a potent risk fac¬tor for myocardial infarction. Nature 1992;359(6396):641-4.
9. Gumprecht J, Zychma MJ, Grzeszczak W, Zukowska-Szczechows-ka E and End-Stage Renal Disease Study Group. Angiotensin I-converting enzyme gene insertion/deletion and angiotensinogen M235T polymorphisms: risk of chronic renal failure. Kidney Int
2000;58(2):513-9.
10. Lalouel JM, Rohrwasser A, Terreros D, Morgan T, Ward K. Angi-otensinogen in essential hypertension: from genetics to nephro-
logy. J Am Soc Nephrol 2001;12(3):606-15.
11. Hernandez D, Linares J, Salido E, et al. Role of ACE gene poly¬morphism on cardiovascular complications after renal transplanta¬tion. Transplant Proc 2001;33(7-8):3686-7.
12. Broekroelofs J, Stegeman CA, Navis G, Tegzess AM, De Zeeuw D, De Jong PE. Risk factors for long-term renal survival after renal transp¬lantation: a role for angiotensin I-converting enzyme gene (inserti¬on/deletion) polymorphism? J Am Soc Nephrol 1998; 9(11): 2075-81.
13. Barocci S, Ginevri F, Valente U, Torre F, Gusmano R, Nocera A. Correlation between angiotensin-converting enzyme gene inserti¬on/deletion polymorphism and kidney graft long-term outcome in pediatric recipients. Transplantation 1999;67(4):534-8.
14. Abdi R, Tran TB, Zee R, Brenner BM, Milford EL. Angiotensin ge¬ne polymorphism as a determinant of posttransplantation renal dysfunction and hypertension. Transplantation 2001;72(4):726-9.
15. Neugebauer S, Baba T, Watanabe T. Association of the nitric oxi¬de synthase gene polymorphism with an increased risk for prog¬ression to diabetic nephropathy in type 2 diabetes. Diabetes. 2000;
49(3):500-3.
16. Hibi K, Ishigami T, Tamura K, et al. Endothelial nitric oxide synthase gene polymorphism and acute myocardial infarction.
Hypertension 1998;32(3):521-6.
17. Lembo G, De Luca N, Battagli C, et al. A common variant of en-dothelial nitric oxide synthase (Glu298Asp) is an independent risk factor for carotid atherosclerosis. Stroke 2001;32(3):735-40.
18. Thomas S, Bruce C, Birkhead A, Wang L. Effect of ecNOS poly¬morphisms and coronary artery disease upon exhaled nitric oxi¬de. J Mol Med 2002;80(3):181-6.
19. Bilsborough W, Green DJ, Mamotte CD, van Bockxmeer FM, O'Driscoll GJ, Taylor RR. Endothelial nitric oxide synthase gene polymorphism, homocysteine, cholesterol and vascular endotheli-al function. Atherosclerosis 2003;169(1):131-8.
20. Ozdemir FN, Akcay A, Atac FB, Micozkadioglu H, Verdi H, Arat Z, Erdal R. Genetic polymorphisms of the renin-angiotensin system and the endothelial constitutive nitric oxide synthase in Turkish end-stage renal disease patients. Nephrol Dial Transplant 2003;18 (supp 4):436.
21. Luther Y, Bantis C, Ivens K, Fehsel K, Kob Bachhofen V, Heering P. Effects of the genetic polymorphisms of the renin-angiotensin system on focal segmental glomerulosclerosis. Kidney Blood Press
Res 2003:26(5-6):333-7.

Thank you for copying data from http://www.arastirmax.com