Esansiyel Hipertansiyonlu Hastalarda M235T Anjiotensinojen Gen Polimorfizmi

Esansiyel hipertansiyon, patogenezinde çeşitli genlerin rol oynadığı poligenik bir hastalıktır. Kan basıncının regülasyonunda görev yapan renin-angiotensin sistemi (RAS) aynı zamanda hipertansiyon gelişimine de neden olabilmektedir. Yapılan çalışmalar neticesinde angiotensinogen (AGT) genin genetik polimorfizm gösterdiği tespit edilmiştir. AGT’ nin en yaygın iki varyantı T174M ve M235T’ dir. Çeşitli populasyonlar üzerinde yapılan çalışmalar sonunda, M235T varyantının diğer varyantlara göre esansiyel hipertyansiyonla daha fazla ilişkili olduğu ifade edilmektedir. Bununla beraber, AGT gen polimorfizminin hipertansiyonla ilişkisi etnik farklılıklar göstermektedir.          105 hipertansif hasta ve 56 normotensif kişiyi kapsayan bu çalışmamızda, Türk populasyonunda AGT 235T varyantının allel frekansı ve esansiyel hipertansiyonla ilişkisi incelenmiştir. MS-PCR’ın (mutagenically seperated polymerase chain reaction) TD PCR (touchdown polimerase chain reaction) formatında kullanıldığında bu çalışmada 235T allel frekansı 0.43 olarak bulunuştur ki bu değer beyaz ırk için tespit edilen değerler ile uyumludur. Çeşitli çalışmalarda bu polimorfizmin esansiyel hipertansiyonla ilişkisi farklı sonuçlar göstermekte olup, çalışmamızda AGT 235T varyantının esansiyel hipertansiyonla anlamlı bir ilişkisi gözlemlenmemiştir (P=0.54). Bununla beraber çalışmamızda hipertansif grupta TT homozigot genotipli hastaların diğer genotipli hastalara (TM+MM) göre anlamlı derecede daha yüksek sistolik kan basıncına sahip oldukları gözlendi (p

Angiotensiınogen Gene Polymorphism in Patients with Essential Hypertension

Essential hypertension is a polygenic disease indicating that several genes are involved in its pathogenesis. The renin-angiotensin  system, which is involved in the regulation of blood pressure, may play an important role in the development of hypertension. It is shown taht the angiotensinogen (AGT) gene had genetic polymorphism and and most common variants of AGT are T174M and M235T. In several studies on varies populations, it was observed that M235T variant is more related witch essential hypertension than other variants. However, the relation between AGT gene polymorphism and hypertension shows ethnic differences. We examined 105 hypertensive patients and 56 normotensive persons to estimate allel frequency of AGT 235T variant and to establish relationship with essential hypertension in Turkish population. In this study, orginally, mutagenically seperated  (MS) PCR  was used in the from of touch down (TD) PCR. Frequency of 235T allel was found 0.43, which accords to previous studies results in whites. Several studies were shown differences about their relation with essential hypertension. In our study we have not observed any significant relationship between the variant of AGT 235T and essential hypertension (P=0.54). However, we observed that hypertensive patients with homozygous T genotype have higher systolic blood pressure than hypertensive patients with other genotype (TM+MM,  p<0.02).

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  • Altun B, Arici M, Nergizoğlu G, Derici Ü, Karatan O, Turgan Ç, et al. Journal of Hypertension, 2005 Patent 2, www.turkhipertansiyon.org , 2012; 23(10): 1817-1823.
  • 2013 ESH/ESC Arteriyel Hipertansiyon Kılavuzu. Türk Kardiyoloji Derneği Arş. 2014; Suppl.(4): 1-72.
  • 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults. Report From the Panel Members Appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014; 311 (5):507-520.
  • Calhoun DA, Bakir SE, Oparil S. Etiology and Pathogenesis of Essential Hypertension. Ann Intern Med. 2003; 139:761-776.
  • Nandhini S. Essential Hypertension –A Review Article. J. Pharm. Sci. & Res. 2014; 6 (9) : 305-307.
  • John Hall. Guyton and Hall Textbook of Medical Physiology: 12th Edition. Saunders Elsevier. ISBN 978-1-4160-4574-8. 2011. 241-242.
  • Liang X, Qiu J, Liu X, Li X, Shaoua Z, Wang J, et al. Polymorphism of Angiotensinogen Gene M235T in Myocardial Infarction and Brain Infarction: a Meta-Analysis. Gene. 2013; 529(1):73–79.
  • Corvol P, Soubrier F, Jeunemaitre X. Molecular Genetics of the Renin-Agiotensin-Aldosterone System in Human Hypertension. Pathol Biol. 1997; 45(3): 229-39.
  • Bedir A, Arik N, Adam B, Kilinc K, Gümüş T, Güner E. Angiotensin Converting Enzyme Gene Polymorphism and Activity in Turkish Patients With Essential Hypertension. Am J Hypertens. 1999; 12(10 Pt 1): 1038-43.
  • Katsuya T, Koike G, Yee T W, Sharp N, Jackson R, Norton R, et al. Association of Angiotensinogen Gene T235 Variant With Increased Risk of Coronary Heart Disease. Lancet 1995; 345:1600– 3.
  • Laragh JH (Ed), Brenner BM (Ed), Jeunemaitr X, Menard J, Clauser E, Corvol P. Angiotensinogen: Molecular Biology and Genetics. Hypertension: Pathophysiology, Diagnosis and Management. Second Edition. Raven Press ISBN 0-78170157-0. New York-1995. pp: 1653-1665.
  • Shamaa M, Fouad H, Haroun M, Hassanein M, Abdel Hay M A. Association Between the Angiotensinogen (AGT) Gene (M235T) Polymorphism and Essential Hypertension in Egyptian Patients. The Egyptian Heart Journal 2015; 67, 1–5.
  • Corvol P, Jeunemaitre X. Molecular Genetics of Human Hypertension: Role of Angiotensinogen. Endocr Rev. 1997; 18(5):662-77.
  • Corvol P, Soubrier F, Jeunemaitre X. Molecular Genetics of the Renin-Angiotensin-Aldosterone System in Human Hypertension. Pathol Biol. 1997;45(3):229-39.
  • Hingorani AD, Sharma P, Jia H, Hopper R, Brown MJ. Blood Pressure and the M235T Polymorphism of the Angiotensinogen Gene. Hypertension 1996; 28(5):907-11.
  • Kılınç K. Yüksek Lisans Tezi “Esansiyel Hipertansiyonlu Hastalarda M235T Anjiotensinojen Gen Polimorfizmi ” Ondokuz Mayıs Ünivesitesi Sağlık Bilimleri Enstitüsü, Tez Danışmanı: Yrd. Doç. Dr. Abdülkerim Bedir. Samsun-1999.
  • Kiema TR, Kauma H, Rantala AO, Lilja M, Reunanen A, Kesaniemi AY, et al. Variation at the Angiotensin-Converting Enzyme Gene and Angiotensinogen Gene Loci in Relation to Blood Pressure Hypertension. 1996; 28(6):1070-5.
  • Schmidt S, Sharma A M, Oliver Z, Beige J, Friedel MW, Ganten D, et al. Association of M235T Variant of Angiotensinogen Gene With Familial Hypertension of Early Onset. Nepfrolohy Dialysis and Transplantation 1995; 10 (7): 1145-1148.
  • Albariño CG, Romanowski V. Phenol Extraction Revisited: a Rapid Method For the Isolation and Preservation of Human Genomic DNA From Whole Blood. Mol Cell Probes 1994; 8(5):423-7.
  • Hamet P, Pausova Z, Adarichev V, Adaricheva K, Tremblay J. Hypertension: Genes and Environment. J Hypertens. 1998;16(4): 397-418.
  • 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) : pp. 169–180.
  • Bennett CL, Schrader AP, Morris BJ. Cross-Sectional Analysis of Met235→Thr Variant of Angiotensinogen Gene in Severe, Familial Hypertension. Biochemical and Biophysical Research Communications. 1993; 197 (2) :833-39
  • Caulfield M, Lavender P, Farrall M, Munroe P, Lawson M, Turner P, et al. Linkage of The Angiotensinogen Gene To Essential Hypertension. The New England Journal Of Medicine. 1994; 330 (23):1629-1633.
  • Cheng JL, Wang AI, Wan J. Association Between the M235T Polymorphism of the AGT Gene and Cytokines in Patients With Hypertension. Exp Ther Med. 2012; 3(3): 509–512.
  • Hata A, Namikawa C, Sasaki M, Sato K, Nakamura T, Lalouel JM, et al. Angiotensinogen as a Risk Factor For Essential Hypertension in Japan. J Clin Invest. 1994 ; 93(3): 1285–1287.
  • Tchelougou D, Kologo JK, Karou SD, Yameogo VN, Bisseye C, Djigma FW, et al. Renin-Angiotensin System Genes Polymorphisms and Essential Hypertension in Burkina Faso, West Africa. International Journal of Hypertension Volume 2015, Article ID 979631, 7 pages http://dx.doi.org/10.1155/2015/979631.
  • Berdeli A, Sekuri C, Sirri Cam F, Ercan E, Sağcan A, İstemihan T, et al. Association Between the eNOS (Glu298Asp) and the RAS Genes Polymorphisms and Premature Coronary Artery Disease in a Turkish Population. Clin Chim Acta. 2005; 351(12): 87-94.
  • Eroglu Z, Cetinkalp S, Erdogan M, Kosova B, Karadeniz M, Kutukculaer A, et al. Association of the Angiotensinogen M235T and Angiotensin Converting Enzyme Insertion/Deletion Gene Polymorphisms in Turkish Type 2 Diabetic Patients With and Without Nephropathy. Journal of Diabetes and Its Complications 2008; 22 (3): 186– 190
  • Koh, KK, Han SH, Oh PC, Shin EK, Quon MJ. Combination Therapy For Treatment or Prevention of Atherosclerosis: Focus on the Lipid-RAAS interaction. Atherosclerosis 2010; 209(2): 307–313.