title: A systematic review of the role of renin angiotensin aldosterone system genes in diabetes mellitus, diabetic retinopathy and diabetic neuropathy.
abstract: BACKGROUND
  The renin angiotensin aldosterone system (RAAS) plays a vital role in regulating glucose metabolism and blood pressure, electrolyte and fluid homeostasis. The aim of this systematic review is to assess the association of the RAAS genes with diabetes mellitus (DM) and its complications of retinopathy, neuropathy and cardiovascular disease (CVD).
  
  
  METHODS
  The relevant English-language studies were identified using the key words of DM, type 1 diabetes mellitus (T1DM), T2DM, renin angiotensin aldosterone polymorphisms or genotypes and RAAS from the search engines of MEDLINE/PubMed, and Scopus from January 1, 1995 to July 30, 2014. Inclusion criteria for selecting relevant studies were reporting the role of RAAS gene variants in the pathogenesis of T1DM or T2DM, diabetic retinopathy (DR), diabetic neuropathy and cardiovascular complication of DM.
  
  
  RESULTS
  The reviewers identified 204 studies of which 73 were eligible for inclusion in the present systematic review. The review indicates the angiotensinogen (AGT) M235T polymorphism might not affect the risk of DM. The role of angiotensin converting enzyme insertion/deletion (ACE I/D) and angiotensin II type 1 receptor gene (AT1R) A1166C polymorphisms in the pathogenesis of DM could not be established. Studies indicate the absence of an association between three polymorphisms of AGT M235T, ACE I/D and AT1R A1166C and DR in DM patients. A protective role for ACE II genotype against diabetic peripheral neuropathy has been suggested. Also, the ACE I/D polymorphism might be associated with the risk of CVD in DM patients.
  
  
  CONCLUSIONS
  More studies with adequate sample size that investigate the influence of all RAAS gene variants together on the risk of DM and its complications are necessary to provide a more clear picture of the RAAS genes polymorphisms involvement in the pathogenesis of DM and its complications.
authors: Department of Clinical Biochemistry, Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran ; Department of Clinical Biochemistry, Medical School, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors: Zohreh
authors: Z
authors: Rahimi
authors: Department of Urology and Regenerative Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors: Mahmoudreza
authors: M
authors: Moradi
authors: Department of Nephrology, Isfahan University of Medical Sciences, Isfahan, Iran.
authors: Hamid
authors: H
authors: Nasri
keywords: Aldosterone; angiotensin; cardiovascular; diabetes mellitus; diabetic neuropathy; diabetic retinopathy; renin; renin angiotensin aldosterone system genes
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