Display options
Share it on

Iran Red Crescent Med J. 2015 Feb 21;17(2):e19469. doi: 10.5812/ircmj.19469. eCollection 2015 Feb.

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.

Iranian Red Crescent medical journal

Mohammad Fathi, Abdol Rahim Nikzamir, Alireza Esteghamati, Manouchehr Nakhjavani, Mir Saeed Yekaninejad

Affiliations

  1. Department of Anesthesiology, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.
  2. 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.
  3. Endocrinology and Metabolism Research Center (EMRC), Vali-e-Asr Hospital, Tehran University of Medical Sciences, Tehran, IR Iran.
  4. Department of Epidemiology and Biostatistics, Tehran University of Medical Sciences, Tehran, IR Iran.

PMID: 25834741 PMCID: PMC4376980 DOI: 10.5812/ircmj.19469

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).

OBJECTIVES: 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).

PATIENTS AND 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.

Keywords: Albuminuria; Diabetes Mellitus; Genetic Polymorphism; Vascular Endothelial Growth Factor

References

  1. Kidney Int. 2006 May;69(9):1654-61 - PubMed
  2. Diabetologia. 1996 Aug;39(8):940-5 - PubMed
  3. Diabet Med. 2003 Aug;20(8):677-82 - PubMed
  4. Kidney Int. 1986 Oct;30(4):538-45 - PubMed
  5. Clin J Am Soc Nephrol. 2008 Sep;3(5):1511-25 - PubMed
  6. Kidney Blood Press Res. 2003;26(5-6):338-43 - PubMed
  7. J Renin Angiotensin Aldosterone Syst. 2012 Mar;13(1):161-74 - PubMed
  8. Nephrol Dial Transplant. 2005 Nov;20(11):2427-32 - PubMed
  9. Exp Clin Endocrinol Diabetes. 2001;109 Suppl 2:S424-37 - PubMed
  10. J Am Soc Nephrol. 1996 May;7(5):661-6 - PubMed
  11. Nephrol Dial Transplant. 2007 Mar;22(3):827-32 - PubMed
  12. Am J Physiol. 1977 Jul;233(1):F13-21 - PubMed
  13. J Lab Clin Med. 1995 Oct;126(4):342-9 - PubMed
  14. Genes (Basel). 2013 Nov 05;4(4):596-619 - PubMed
  15. Diabetes. 2004 Mar;53(3):861-4 - PubMed
  16. Kidney Int Suppl. 2000 Sep;77:S113-9 - PubMed
  17. Endocr Rev. 1997 Feb;18(1):4-25 - PubMed
  18. Kidney Int. 2004 Jun;65(6):2003-17 - PubMed
  19. J Clin Hypertens (Greenwich). 2001 Mar-Apr;3(2):99-102 - PubMed
  20. Kidney Int. 2006 Apr;69(8):1293-5 - PubMed
  21. Nat Rev Nephrol. 2010 Jun;6(6):361-70 - PubMed
  22. Horm Metab Res. 1998 May;30(5):276-80 - PubMed
  23. Hum Reprod. 2008 Jan;23(1):211-5 - PubMed
  24. Nephrol Dial Transplant. 1997 Mar;12(3):427-9 - PubMed
  25. Adv Chronic Kidney Dis. 2005 Apr;12(2):146-54 - PubMed
  26. Am J Kidney Dis. 2005 Feb;45(2):288-94 - PubMed
  27. Diabetologia. 1990 Jul;33(7):438-43 - PubMed
  28. Nat Clin Pract Nephrol. 2008 Apr;4(4):216-26 - PubMed
  29. J Renin Angiotensin Aldosterone Syst. 2008 Mar;9(1):32-6 - PubMed
  30. Am J Kidney Dis. 2002 Sep;40(3):489-94 - PubMed
  31. Transl Res. 2011 Aug;158(2):85-91 - PubMed
  32. Am J Hum Genet. 1992 Jul;51(1):197-205 - PubMed
  33. Endocr J. 2010;57(5):431-8 - PubMed
  34. Ophthalmic Res. 1995;27(1):48-52 - PubMed
  35. Am J Physiol Heart Circ Physiol. 2001 Feb;280(2):H885-91 - PubMed
  36. Kidney Int. 1995 Apr;47(4):1176-81 - PubMed
  37. Lab Invest. 1995 Jun;72(6):615-8 - PubMed
  38. Kidney Int. 2004 Nov;66(5):2095-106 - PubMed
  39. J Am Soc Nephrol. 2001 May;12(5):993-1000 - PubMed
  40. Am J Physiol Heart Circ Physiol. 2004 Jun;286(6):H2096-102 - PubMed
  41. Clin Chim Acta. 2010 Nov 11;411(21-22):1688-93 - PubMed

Publication Types