title: Combination of Angiotensin Converting Enzyme Insertion/Deletion (I/D) (rs4646994) and VEGF Polymorphism (+405G/C; rs2010963) Synergistically Associated With the Development, of Albuminuria in Iranian Patients With Type 2 Diabetes.
abstract: BACKGROUND
  Angiotensin-converting enzyme (ACE) insertion/deletion (I/D) and vascular endothelial growth factor (VEGF) polymorphisms have been shown to associate with diabetic nephropathy (DN).
  
  
  OBJECTIVE
  We examined the hypothesis that ACE-D and VEGF-G alleles act synergistically in association with DN, in patients with type 2 diabetes mellitus (T2DM).
  
  
  METHODS
  The VEGF (rs2010963) and ACE (rs4646994) genotypes were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 490 T2DM patients. Diabetic patients were classified as T2DM patients with and without albuminuria (control). The PCR and RFLP were used to detect the VEGF and ACE alleles.
  
  
  RESULTS
  A total of 255 consecutive patients with T2DM and microalbuminuria (Group A) and 235 patients with T2DM and normoalbuminuria (Group B) were included in the study. In univariate analysis, the groups were statistically similar for all variables, except for glycated hemoglobin (HbA1c) (P = 0.034), and the frequency of ACE (P = 0.015) and VEGF (P = 0.006) genotypes. Our study showed that the VEGF-G and ACE-D alleles are independently associated with the development of nephropathy. According to our data, the combination of these two risk factors had a significant synergistic effect on the risk of microalbuminuria development.
  
  
  CONCLUSIONS
  Our study indicated that ACE-D and VEGF-G alleles can be an independent risk factor for microalbominuria in T2DM patients.
authors.affiliation: Department of Anesthesiology, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Fathi
authors.affiliation: Department of Biochemistry, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran ; Endocrinology and Metabolism Research Center (EMRC), Vali-e-Asr Hospital, Tehran University of Medical Sciences, Tehran, IR Iran.
authors.forename: Abdol Rahim
authors.initials: AR
authors.lastname: Nikzamir
authors.affiliation: Endocrinology and Metabolism Research Center (EMRC), Vali-e-Asr Hospital, Tehran University of Medical Sciences, Tehran, IR Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Esteghamati
authors.affiliation: Endocrinology and Metabolism Research Center (EMRC), Vali-e-Asr Hospital, Tehran University of Medical Sciences, Tehran, IR Iran.
authors.forename: Manouchehr
authors.initials: M
authors.lastname: Nakhjavani
authors.affiliation: Department of Epidemiology and Biostatistics, Tehran University of Medical Sciences, Tehran, IR Iran.
authors.forename: Mir Saeed
authors.initials: MS
authors.lastname: Yekaninejad
keywords: Albuminuria; Diabetes Mellitus; Genetic Polymorphism; Vascular Endothelial Growth Factor
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