Lack of association between renin-angiotensin system (RAS) polymorphisms and hypertension in tunisian type 2 diabetics


Imen Arfa
Sonia Nouira
Abdelmajid Abid
Nissaf Bouafif-Ben Alaya
Mohamed Majdi Zorgati
Dhafer Malouche
Imen Manai
Mohamed Chiheb Ben Rayana
Samira Blousa-Chabchoub
Habiba Ben Romdhane
Mohammed Slim Ben Ammar
Afif Ben Salah
Sonia Abdelhak


Background :The genes encoding renin-angiotensin system (RAS) components are potent candidate genes in both hypertension and diabetes namely ACE encoding the angiotensin converting enzyme and AGT encoding angiotensinogen. It has been suggested that the insertion/deletion (I/D) polymorphism in intron 16 of ACE gene is associated with ACE levels, and M235T gene polymorphism is associated with plasma AGT levels.
Aim : We examined in this report the association between ACE I/D and AGT M235T polymorphisms with hypertension status in Tunisian type 2 diabetic subjects.
Methods:Thirty nine hypertensive and 22 normotensive type 2 diabetic Tunisian patients were recruited for this study. The I/D polymorphism of ACE gene was analysed with nested PCR in order to avoid mistyping heterozygous individuals and the M235T polymorphism of AGT gene was analysed using PCR and allele
specific restriction.
Results:The distribution of DD, ID and II genotypes did not significantly differ between type 2 diabetic patients with or without hypertension (DD: 49%; ID: 41%; II: 10% vs DD: 36%; ID: 55 %; II: 9%, respectively) (¯2=1.06, p=0.58). There was also no significant statistical difference between these two groups for the M235T polymorphism (TT: 20%; MT: 54%; MM: 26% vs TT: 27%; MT: 41 %; MM: 32%, respectively) (¯2=0.95, p=0.62)
Conclusion:RAS polymorphisms do not seem to play a role in the development of hypertension in the studied Tunisian type 2 diabetic subjects.


Hypertension, Type 2 diabetes (T2D), Polymorphism, Reninangiotensin system (RAS)



  1. Flack JM, Peters R, Shafi T et al. Prevention of hypertension and its complications: theoretical basis and guidelines for treatment. J Am Soc Nephrol 2003;14: 92-8.2. Kurtz TW, Spence MA. Genetics of essential hypertension. Am J Med 1993; 94: 77-84.
  2. Barnett AH, Eff C, Leslie RD, Pyke DA. Diabetes in identical twins. A study of 200 pairs. Diabetologia 1981; 20: 87-93.
  3. Swales JD, Dzau VJ. Angiotensin-converting enzyme inhibition: research advances and clinical implications. J Am Heart 1992; 123: 1412-1413.
  4. Aguilar D, Solomon SD. ACE inhibitors and angiotensin receptor antagonists and the incidence of new-onset diabetes mellitus: an emerging theme. Drugs 2006; 66: 1169-1177.
  5. Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest 1990; 86: 1343-1346.
  6. Huang W, Gallois Y, Bouby N et al. Genetically increased angiotensin I-converting enzyme level and renal complications in the diabetic mouse. Proc Natl Acad Sci U S A. 2001; 98: 13330- 13334.