Variability of Angiotensinogen and Susceptibility to Multiple Sclerosis

Czech version

Authors: M. Hladíková ¹; P. Štourač1 ^,2; A. Vašků ³; Y. Benešová ¹
Authors‘ workplace: Neurologická klinika LF MU a FN Brno ¹; CEITEC MU, Brno ²; Ústav patologické fyziologie LF MU, Brno ³
Published in: Cesk Slov Neurol N 2012; 75/108(1): 38-43
Category: Original Paper

Overview

Aim:
To investigate whether there is an association between (–6)A/G a M235T polymorphisms of angiotensinogen (ATG) and susceptibility to multiple sclerosis and/or the course of the disease.

Materials and methods:
A total of 195 patients (49 men and 146 women) with multiple sclerosis (MS) and 126 healthy controls were investigated for two angiotensinogen polymorphisms using PCR and restriction analysis. The data were analysed with the support Statistica software, version 8.0 (StratSoft, Inc., Tulsa, OK, USA) and using the Fisher’s, Chi-squared and Holm’s tests.

Results:
We observed no significant differences in genotype or allelic distribution between groups of patients and control subjects for tested ATG polymorphisms. Double homozygotes MMGG were less frequent in the group of MS patients (p = 0.029, Odds ratio = 0.57, CI 0.33–0.98). However, using the Holm’s test for multiple comparisons, the results lacked statistical significance (p_corr= 0.17). We did not find significant differences either in genotype distribution or in allele frequencies among MS patients with the different disease courses.

Conclusions:
Our study did not find an association between (–6)A/G a M235T polymorphisms of ATG and susceptibility to multiple sclerosis or the course of this disease.

Key words:
multiple sclerosis – renin-angiotensin system – angiotensinogen – polymorphism

Sources

1. Miller DH, Barkhof F, Berry I, Kappos L, Scotti G, Thompson AJ. Magnetic resonance imaging in monitoring the treatment of multiple sclerosis: concerted action guidelines. J Neurol Neurosurg Psychiatry 1991; 54(8): 683–688.

2. Thorpe JW, Kidd D, Moseley IF, Kenndall BE, Thompson AJ, MacManus DG et al. Serial gadolinium-enhanced MRI of the brain and spinal cord in early relapsing-remitting multiple sclerosis. Neurology 1996; 46(2): 373–378.

3. Das UN. Is angiotensin-II an endogenous pro-inflammatory molecule? Med Sci Monit 2005; 11(5): 155–162.

4. Suzuki Y, Ruiz-Ortega M, Lorenzo O, Ruperez M, Esteban V, Egido J. Inflammation and angiotensin II. Int J Biochem Cell Biol 2003; 35(6): 881–900.

5. Wick G, Knoflach M, Xu Q. Autoimmune and inflammatory mechanisms in atherosclerosis. Annu Rev Immunol 2004; 22: 361–403.

6. Feldmann M, Steinman L. Design of effective immunotherapy for human autoimmunity. Nature 2005; 435(7042): 612–619.

7. Fyhrquist F, Saijonmaa O. Renin-angiotensin system revisited. J Intern Med 2008; 264(3): 224–236.

8. Zhuo J, Moeller I, Jenkins T, Chai SY, Allen AM, Ohishi M et al. Mapping tissue angiotensin-converting enzyme and angiotensin AT1, AT2 and AT4 receptors. J Hypertens 1998; 16(12): 2027–2037.

9. Stegbauer J, Lee DH, Seubert S, Ellrichmann G, Manzel A, Kvakan H et al. Role of the renin-angiotensin system in autoimmune inflammation of the central nervous system. Proc Natl Acad Sci U S A 2009; 106(35): 14942–14947.

10. Platten M, Youssef S, Hur EM, Ho PP, Han MH, Lanz TV et al. Blocking angiotensin-converting enzyme induces potent regulatory T cells and modulates TH1- and TH17-mediated autoimmunity. Proc Natl Acad Sci U S A 2009; 106(35): 14948–14953.

11. Constantinescu CS, Ventura E, Hilliard B, Rostami A. Effects of the angiotensin converting enzyme inhibitor captopril on experimental autoimmune encephalomyelitis. Immunopharmacol Immunotoxicol 1995; 17(3): 471–491.

12. Ottervald J, Franzén B, Nilsson K, Andersson LI, Khademi M, Eriksson B et al. Multiple sclerosis: Identification and clinical evaluation of novel CSF biomarkers. J Proteomics 2010; 73(6): 1117–1132.

13. Hammack BN, Fung KY, Hunsucker SW, Duncan MW, Burgoon MP, Owens GP et al. Proteomic analysis of multiple sclerosis cerebrospinal fluid. Mult Scler 2004; 10(3): 245–260.

14. Stoop MP, Dekker LJ, Titulaer MK, Lamers RJ, Burgers PC, Sillevis Smitt PA et al. Quantitative Matrix-Assisted Laser Desorption Ionization-Fourier Transform Ion Cyclotron Resonance (MALDIFT-ICR) Peptide Profiling and Identification of Multiple-Sclerosis-Related Proteins. J Proteome Res 2009; 8(3): 1404–1414.

15. Igić R, Behnia R. Properties and distribution of angiotensin I converting enzyme. Curr Pharm Des 2003; 9(9): 697–706.

16. Imboden H, Harding JW, Hilgenfeldt U, Celio MR, Felix D. Localization of angiotensinogen in multiple cell types of rat brain. Brain Res 1987; 410(1): 74–77.

17. Inoue I, Nakajima T, Williams CS, Quackenbush J, Puryear R, Powers M et al. A nucleotide substitution in the promoter of human angiotensinogen is associated with essential hypertension and affects basal transcription in vitro. J Clin Invest 1997; 99(7): 1786–1797.

18. Rotimi C, Cooper R, Ogunbiyi O, Morrison L, Ladipo M, Tewksbury D et al. Hypertension, serum angiotensinogen, and molecular variants of the angiotensinogen gene among Nigerians. Circulation 1997 20; 95(10): 2348–2350.

19. Jeunemaitre X, Soubrier F, Kotelevtsev YV, Lifton RP, Williams CS, Charru A et al. Molecular basis of human hypertension: role of angiotensinogen. Cell 1992; 71(1): 169–180.

20. Polman CH, Reingold SC, Edan G, Filippi M, Hartung HP, Kappos L et al. Diagnostic criteria for multiple sclerosis: 2005 revisions to the „McDonald Criteria“. Ann Neurol 2005; 58(6): 840–846.

21. Sambrook J., Maniatis T, Fritsch EF. Molecular Cloning: a Laboratory Manual. New York: Cold Spring Harbor Laboratory Press 1989.

22. Russ AP, Maerz W, Ruzicka V, Stein U, Gross W. Rapid detection of the hypertension-associated Met235-->Thr allele of the human angiotensinogen gene. Hum Mol Genet 1993; 2(5): 609–610.

23. Hegele RA, Harris SB, Hanley AJ, Sun F, Connelly PW, Zinman B. –6A promoter variant of angiotensinogen and blood pressure variation in Canadian Oji-Cree. J Hum Genet 1998; 43(1): 37–41.

24. Lovrečić L, Ristić S, Starcević-Cizmarević N, Jazbec SS, Sepcić J, Kapović M et al. Angiotensin-converting enzyme I/D gene polymorphism and risk of multiple sclerosis. Acta Neurol Scand 2006; 114(6): 374–377.

25. Constantinescu CS, Goodman DB, Grossman RI, Mannon LJ and Cohen JA. Serum angiotensin-converting enzyme in multiple sclerosis. Arch Neurol 1997; 54(8): 1012–1015.

26. Choi YS, Kwon H, Kim JH, Shin JE, Choi Y, Yoon TK. Haplotype-based association of ACE I/D, AT1R 1166A>C, and AGT M235T polymorphisms in renin-angiotensin-aldosterone system genes in Korean women with idiopathic recurrent spontaneous abortions. Eur J Obstet Gynecol Reprod Biol 2011; 158(2): 225–228.

27. Yanai K, Saito T, Hirota K, Kobayashi H, Murakami K, Fukamizu A. Molecular variation of the human angiotensinogen core promoter element located between the TATA box and transcription initiation site affects its transcriptional activity. J Biol Chem 1997; 272(48): 30558–30562.

28. Brasier AR, Li J. Mechanisms for inducible control of angiotensinogen gene transcription. Hypertension 1996; 27(3): 465–475.

29. Hoffjan S, Akkad DA. The genetics of multiple sclerosis: an update 2010. Mol Cell Probes 2010; 24(5): 237–243.