Ali BAYRAMA, Mehri İĞCİ, Remzi YİĞİTER, Mehmet Ali ELÇİ, Beyhan CENGIZ, Serdar ÖZTUZCU, Yusuf Ziya İĞCİ, Mustafa ULAŞLI, Recep BAYRAKTAR, İbrahim BOZGEYİK, Ecir Ali ÇAKMAK, Ahmet ARSLAN

Multiple Sklerozlu Hastalarda NOS3 Geninin mRNA Seviyesinde İfadesi

Amaç: Merkezi sinir sisteminde demiyelinizasyon ve akson hasarı ile oluşan multiple sklerozun (MS) gelişiminde genetik etmenlerin de rol alabileceği düşünülmektedir. Nitrik Oksit Sentazın (NOS) nöron koruyucu etkinliği olduğunu gösteren çeşitli çalışmalar yapılmıştır. NOS ailesinden NOS3'ün (eNOS) NOS1 ve 2'nin aksine artan gen ifadesinin nörotoksik etki göstermediği, koruyucu özelliği olduğu bilinmektedir. Bu nedenle bu çalışmada NOS3 geninin ifade düzeyinin MS hastalığı ile ilişkisinin araştırılması amaçlanmıştır. Gereç ve Yöntem: Gaziantep Üniversitesi Tıp Fakültesi Şahinbey Araştırma ve Uygulama Hastanesi Nöroloji Polikliniği'nde takip edilen 17-65 yaşları arası 93 MS hastası çalışma kapsamına alındı. Kontrol grubunu 93 sağlıklı gönüllü oluşturdu. MS'li hasta grubunda yaş ortalaması 35.60 (en küçük:17, en büyük:65); kontrol grubunda ise 33.80 (en küçük:20, en büyük:73) olarak bulundu. Real Time PCR yöntemi ile çalışma yapıldı. Bulgular: NOS3 genindeki NOS3*2, NOS3*3 ve NOS3*4 allellerinde gen ifadesinin hasta/kontrol gruplarında anlamlı olarak düştüğü gözlemlenmiş ve gruplar arasındaki farklar Mann-Whitney yöntemi ile %95 güven aralığında (p

mRNA Expressions of NOS3 Gene among Patients with Multiple Sclerosis

Objective: It is considered that genetic factors may play a role in the development of MS, which is caused by demyelination and axonal damage in central nervous system. Several studies, showing that NOS has a neuroprotective activism, have been conducted. It is known that, contrary to NOS1 ve 2, gene expression of NOS3 from NOS family does not show neurotoxic effect, but has a protective activism. Therefore, this study aimed to investigate the relationship of NOS3 gene expression levels with MS disease. Material and Method: 93 MS patients between the ages of 17-65 were examined in the study at Gaziantep University school of medicine, Sahinbey Research and Application Hospital Neurology Department. The control group consisted of 93 healthy volunteers. It was found that the mean age of patients with MS was 35.60 and in the control group was 33.80. The study was conducted with RT-PCR method. Results: The gene expression in alleles of NOS3*2, NOS3*3, and NOS3*4 in NOS3 patient/control groups were observed to decrease significantly, and the differences between groups with the Mann-Whitney method within 95% confidence interval (p

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1. Stewart S, Hart CL, Hole DJ, McMurray JJ. Population prevalence, incidence, and predictors of atrial fibrillation in the Renfrew/Paisley study. Heart 2001; 86: 516-21.
2. Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG. Multiple sclerosis. N Eng J Med 2000; 343: 938-52.
3. Confavreux C, Aimard G, Devic M. Course and prognosis of multipl sclerosis assessed by the computerized data processing of 349 patients. Brain 1980 and 1980; 103: 281-300.
4. Kurtzke JF. A reassessment of the distribution of multiple sclerosis. Parts I and II. Acta Neurol Scand Vols Scand 1975; 51: 110-57.
5. Ebers GC, Sadovnick AD. Epidemiology. Multiple sclerosis 1997: 5-28.
6. Altıntaş A, Kantarcı O, Siva A. Multiple sklerozda sitokinlerin rolü. Türk Nörol Derg 1995; 4: 167-71.
7. Förstermann U, Closs EI, Pollock JS, Nakane M, Schwarz P, Gath I, Kleinert H. Nitric oxide synthase isozymes. Characterization, purification, molecular cloning, and functions. Hypertension 1994; 1121-31.
8. Endres M, Laufs U, Liao JK, Moskowitz MA. Targeting eNOS for stroke protection. Trends Neurosci 2004; 283-9.
9. Berner M, Beghetti M, Ricou B, Rauge JC, Pretne R, Friedli B. Relief of severe pulmonary hypertension after clousure of a large ventricular septal defect using low dose ınhaled nitric oxide synthase ındicating a neural role for nitric oxide. Nature 1990; 347: 768-70.
10. Moncada S, Higgs A. The L-Arginin Nitric Oxide Pathway. N Engl J Med 1993; 329: 2002-12.
11. Anggard E. Nitric oxide: mediator, murderer and medicine. The Lancet 1994; 343: 1199-206.
12. Berner M, Beghetti M, Ricou B, Rauge JC, Pretne R, Friedli B. Relief of severe pulmonary hypertension after clousure of a large ventricular septal defect using low dose ınhaled nitric oxide synthase ındicating a neural role for nitric oxide. Nature 1990; 347: 768-70.
13. Koh PO. Ferulic acid modulates nitric oxide synthase expression in focal cerebral ischemia. 2012; 273-8.
14. Defer GL, Barre J, Ledudal P, Tillement JP, Degos JD. Methylprednisolone infusion during acute exacerbation of MS: plasma and CSF concentrations. Eur Neurol 1995; 35: 143-8.
15. Yılmaz, NÇ. Multipl Skleroz ve Otoimmünite. 2006, Sağlık Bakanlığı Haydarpaşa Numune Eğitim ve Araştırma Hastanesi, Uzmanlık Tezi, 91 sayfa, İstanbul (Doç. Dr. Hulya TİRELİ). Altıntaş A, Benbir G. Miyelinizasyon, Demiyelinizasyon Ve Remiyelinizasyon Mekanizmaları. Turk Nöroloji Dergisi 2005; 2.
16. Conzales GG, Avellana-Adalid V, Alli C, Baron Van Evercooren A. Myelination of the central nervous system, From Basic Immunology to Immun-Mediated Demyelination. Springer-Verlag 1999; 101-15.
17. Yun HY, Dawson VL , Dawson TM. Nitric oxide in health and disease of the nervous system. Mol Psychiatry 1997; 2: 300-10.
18. Szabo C. Physiological and pathophysiological roles of nitric oxide in the central nervous system. Brain Res Bull 1996; 41: 131-41.
19. Yun HY, Dawson VL, Dawson TM. Neurobiology of nitric oxide. Crit Rev Neurobiol 1996; 10: 291-316.
20. Vane JR, Mitchell JA, Appleton I, et al. Inducible isoforms of cyclooxygenase and nitric-oxide synthase in inflammation. Proc Natl Acad Sci USA 1994; 91: 2046-50.
21. Galea E, Reis DJ, Xu H, Feinstein DL. Transient expression of calcium-independent nitric oxide synthase in blood vessels during brain development. FASEB J 1995; 9: 1632-7.
22. Sparrow JR. Inducible nitric oxide synthase in the central nervous system. J Mol Neurosci 1994-1995; 5: 219-9.
23. Hashiguchi A, Yano S, Morioka M, Hamada J, Ushio Y, Takeuchi Y, Fukunaga K. Up-regulation of endothelial nitric oxide synthase via phosphatidylinositol 3-kinase pathway contributes to ischemic tolerance in the CA1 subfield of gerbil hippocampus. J Cereb Blood Flow Metab 2004; 24: 271-9.
24. Koh PO. Ferulic acid modulates nitric oxide synthase expression in focal cerebral ischemia. Lab Anim Res 2012; 28: 273-8.
25. Heeringa P, Steenbergen E, van Goor H. A protective role for endothelial nitric oxide synthase in glomerulonephritis. Kidney Int 2002; 61: 822-5.
26. Groves JT. Peroxynitrite: Reactive, invasive and enigmatic. Curr Opin Chem Biol 1999; 3: 226-355.