Molecular Biology Reports

, Volume 39, Issue 2, pp 1293–1303 | Cite as

Association between two genetic polymorphisms of the renin-angiotensin-aldosterone system and diabetic nephropathy: a meta-analysis

  • Wei Ding
  • Furu Wang
  • Qiaoqiao Fang
  • Minmin Zhang
  • Jing Chen
  • Yong Gu
Article

Abstract

The widely studied candidate genes of the renin-angiotensin-aldosterone system, angiotensinogen (AGT), and angiotensin II receptor type 1 (AGTR1), are implicated in the development of diabetic nephropathy (DN). A number of studies have evaluated the association between the functional polymorphisms, AGT M235T and AGTR1 A1166C, and DN risk with conflicting results. The present meta-analysis was performed to estimate the overall risk of these polymorphisms associated with DN on 4,377 DN cases and 4,905 controls from 34 published case–control studies by searching electronic databases and reference lists of relevant articles. We examined the association between each polymorphism and the risk of DN by odds ratio (OR) with 95% confidence intervals (95% CI) and calculated the ORs for different genetic model. In addition, stratification analysis by ethnicity and diabetes mellitus (DM) type was conducted. In this meta-analysis, we failed to find any significant main effects in both overall analysis and stratified analysis for the AGT M235T. However, the overall analysis detected a significant association between the AGTR1 A1166C and the risk of DN for the CC compared with the AA and dominant genetic model (CC vs. AA: OR = 2.10, 95% CI: 1.00–4.44; dominant model: OR = 2.11, 95% CI: 1.06–4.23). In subgroup analysis, only patients with T2DM showed significant association for CC vs. AA model and dominant model (CC vs. AA: OR = 3.31, 95% CI: 1.21–9.08; dominant model: OR = 3.50, 95% CI: 1.41–8.69). This study suggests that the AGTR1 A1166C polymorphism may contribute to DN development, particularly in T2DM patients.

Keywords

RAAS Polymorphisms AGT M235T AGTR1 A1166C Diabetic nephropathy Genetic epidemiology 

Supplementary material

11033_2011_862_MOESM1_ESM.doc (104 kb)
Supplementary material 1 (DOC 103 kb)

References

  1. 1.
    Schmidt S, Ritz E (1997) Genetics of the renin-angiotensin system and renal disease: a progress report. Curr Opin Nephrol Hypertens 6:146–151PubMedGoogle Scholar
  2. 2.
    Burns KD (2000) Angiotensin II and its receptors in the diabetic kidney. Am J Kidney Dis 36:449–467PubMedGoogle Scholar
  3. 3.
    Kim S, Iwao H (2000) Molecular and cellular mechanisms of angiotensin II-mediated cardiovascular and renal diseases. Pharmacol Rev 52:11–34PubMedGoogle Scholar
  4. 4.
    Rahimi Z et al (2011) The frequency of factor V Leiden mutation, ACE gene polymorphism, serum ACE activity and response to ACE inhibitor and angiotensin II receptor antagonist drugs in Iranians type II diabetic patients with microalbuminuria. Mol Biol Rep 38:2117–2123. doi:10.1007/s11033-010-0338-1 PubMedGoogle Scholar
  5. 5.
    Gumprecht J et al (2000) Angiotensin I-converting enzyme gene insertion/deletion and angiotensinogen M235T polymorphisms: risk of chronic renal failure. End-Stage Renal Disease Study Group. Kidney Int 58:513–519. doi:10.1046/j.1523-1755.2000.00197.x PubMedGoogle Scholar
  6. 6.
    Lovati E et al (2001) Genetic polymorphisms of the renin-angiotensin-aldosterone system in end-stage renal disease. Kidney Int 60:46–54. doi:10.1046/j.1523-1755.2001.00769.x PubMedGoogle Scholar
  7. 7.
    Wang WY, Zee RY, Morris BJ (1997) Association of angiotensin II type 1 receptor gene polymorphism with essential hypertension. Clin Genet 51:31–34PubMedGoogle Scholar
  8. 8.
    Jeunemaitre X et al (1992) Molecular basis of human hypertension: role of angiotensinogen. Cell 71:169–180. doi:10.1016/0092-8674(92)90275-H PubMedGoogle Scholar
  9. 9.
    Caulfield M et al (1994) Linkage of the angiotensinogen gene to essential hypertension. N Engl J Med 330:1629–1633PubMedGoogle Scholar
  10. 10.
    Lindholm LH et al (2002) Cardiovascular morbidity and mortality in patients with diabetes in the Losartan intervention for endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 359:1004–1010. doi:10.1016/S0140-6736(02)08090-X PubMedGoogle Scholar
  11. 11.
    Fogarty DG et al (1996) A molecular variant of angiotensinogen is associated with diabetic nephropathy in IDDM. Diabetes 45:1204–1208PubMedGoogle Scholar
  12. 12.
    Crisan D, Carr J (2000) Angiotensin I-converting enzyme: genotype and disease associations. J Mol Diagn 2:105–115PubMedGoogle Scholar
  13. 13.
    Doria A et al (1997) Synergistic effect of angiotensin II type 1 receptor genotype and poor glycaemic control on risk of nephropathy in IDDM. Diabetologia 40:1293–1299. doi:10.1007/s001250050823 PubMedGoogle Scholar
  14. 14.
    Miller JA, Thai K, Scholey JW (2000) Angiotensin II type 1 receptor gene polymorphism and the response to hyperglycemia in early type 1 diabetes. Diabetes 49(9):1585–1589. doi:10.2337/diabetes.49.9.1585 PubMedGoogle Scholar
  15. 15.
    Gallego PH et al (2008) Angiotensinogen gene T235 variant: a marker for the development of persistent microalbuminuria in children and adolescents with type 1 diabetes mellitus. J Diabetes Complicat 22:191–198. doi:10.1016/j.jdiacomp.2007.03.003 PubMedGoogle Scholar
  16. 16.
    Gutierrez JA et al (1997) Superoxide anions contribute to impaired regulation of blood pressure by nitric oxide during the development of cardiomyopathy. J Pharmacol Exp Ther 282:1643–1649PubMedGoogle Scholar
  17. 17.
    Rogus JJ et al (1998) Diabetic nephropathy is associated with AGT polymorphism T235: results of a family-based study. Hypertension 31:627–631. http://hyper.ahajournals.org/cgi/content/full/31/2/627 Google Scholar
  18. 18.
    Tomino Y et al (1999) Relationship between polymorphism in the angiotensinogen, angiotensin-converting enzyme or angiotensin II receptor and renal progression in Japanese NIDDM patients. Nephron 82:139–144. doi:10.1159/000045390 PubMedGoogle Scholar
  19. 19.
    Miura J et al (1999) Genetic polymorphism of renin-angiotensin system is not associated with diabetic vascular complications in Japanese subjects with long-term insulin dependent diabetes mellitus. Diabetes Res Clin Pract 45(1):41–49PubMedGoogle Scholar
  20. 20.
    van Ittersum FJ et al (2000) Genetic polymorphisms of the renin-angiotensin system and complications of insulin-dependent diabetes mellitus. Nephrol Dial Transplant 15:1000–1007. doi:10.1093/ndt/15.7.1000 PubMedGoogle Scholar
  21. 21.
    Fradin S et al (2002) Relationship between polymorphisms in the renin-angiotensin system and nephropathy in type 2 diabetic patients. Diabetes Metab 28:27–32. doi:DM-02-2002-28-1-1262-3636-101019-ART4 PubMedGoogle Scholar
  22. 22.
    Chang HR et al (2003) Study of the polymorphism of angiotensinogen, anigiotensin-converting enzyme and angiotensin receptor in type II diabetes with end-stage renal disease in Taiwan. J Chin Med Assoc 66:51–56PubMedGoogle Scholar
  23. 23.
    Prasad P et al (2006) Chronic renal insufficiency among Asian Indians with type 2 diabetes: I. Role of RAAS gene polymorphisms. BMC Med Genet 7:42PubMedGoogle Scholar
  24. 24.
    Buraczynska M et al (2006) Genetic polymorphisms of the renin-angiotensin system in end-stage renal disease. Nephrol Dial Transplant 21:979–983. doi:10.1093/ndt/gfk012 PubMedGoogle Scholar
  25. 25.
    Mollsten A et al (2008) The effect of polymorphisms in the renin-angiotensin-aldosterone system on diabetic nephropathy risk. J Diabetes Complicat 22:377–383. doi:10.1016/j.jdiacomp.2007.06.005 PubMedGoogle Scholar
  26. 26.
    Eroglu Z et al (2008) Association of the angiotensinogen M235T and angiotensin-converting enzyme insertion/deletion gene polymorphisms in Turkish type 2 diabetic patients with and without nephropathy. J Diabetes Complicat 22:186–190. doi:10.1016/j.jdiacomp.2006.12.004 PubMedGoogle Scholar
  27. 27.
    Tien KJ et al (2009) Gender-dependent effect of ACE I/D and AGT M235T polymorphisms on the progression of urinary albumin excretion in Taiwanese with type 2 diabetes. Am J Nephrol 29:299–308. doi:10.1159/000163592 PubMedGoogle Scholar
  28. 28.
    Ahluwalia TS et al (2009) ACE variants interact with the RAS pathway to confer risk and protection against type 2 diabetic nephropathy. DNA Cell Biol 28:141–150. doi:10.1089/dna.2008.0810 PubMedGoogle Scholar
  29. 29.
    Osawa N et al (2007) Combinational effect of genes for the renin-angiotensin system in conferring susceptibility to diabetic nephropathy. J Hum Genet 52:143–151. doi:10.1007/s10038-006-0090-5 PubMedGoogle Scholar
  30. 30.
    Zychma MJ et al (2000) Angiotensinogen M235T and chymase gene CMA/B polymorphisms are not associated with nephropathy in type II diabetes. Nephrol Dial Transplant 15:1965–1970. doi:10.1093/ndt/15.12.1965 PubMedGoogle Scholar
  31. 31.
    Zintzaras E, Lau J (2008) Synthesis of genetic association studies for pertinent gene-disease associations requires appropriate methodological and statistical approaches. J Clin Epidemiol 61:634–645. doi:10.1016/j.jclinepi.2007.12.011 PubMedGoogle Scholar
  32. 32.
    Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558. doi:10.1002/sim.1186 PubMedGoogle Scholar
  33. 33.
    Egger M et al (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634PubMedGoogle Scholar
  34. 34.
    Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50:1088–1101PubMedGoogle Scholar
  35. 35.
    Zintzaras E, Papathanasiou AA, Stefanidis I (2009) Endothelial nitric oxide synthase gene polymorphisms and diabetic nephropathy: a HuGE review and meta-analysis. Genet Med 11:695–706. doi:10.1097/GIM.0b013e3181b2046b PubMedGoogle Scholar
  36. 36.
    Harrison-Bernard LM (2009) The renal renin-angiotensin system. Adv Physiol Educ 33:270–274. doi:10.1152/advan.00049.2009 PubMedGoogle Scholar
  37. 37.
    Zhou JB et al (2010) Angiotensin-converting enzyme gene polymorphism is associated with type 2 diabetes: a meta-analysis. Mol Biol Rep 37:67–73. doi:10.1007/s11033-009-9648-6 PubMedGoogle Scholar
  38. 38.
    Anderson PW, Do YS, WA (1993) Hsueh, Angiotensin II causes mesangial cell hypertrophy. Hypertension 21:29–35. http://hyper.ahajournals.org
  39. 39.
    Yip JW et al (1996) Glomerular hyperfiltration in the prediction of nephropathy in IDDM: a 10-year follow-up study. Diabetes 45:1729–1733PubMedGoogle Scholar
  40. 40.
    Feldt-Rasmussen B, Borch-Johnsen K, Mathiesen ER (1985) Hypertension in diabetes as related to nephropathy Early blood pressure changes. Hypertension 7:II18–II20PubMedGoogle Scholar
  41. 41.
    Thomas W et al (2001) Rise in albuminuria and blood pressure in patients who progressed to diabetic nephropathy in the diabetes control and complications trial. J Am Soc Nephrol 12:333–340PubMedGoogle Scholar
  42. 42.
    Reyes-Engel A et al (2006) Influence of gender and genetic variability on plasma angiotensin peptides. J Renin Angiotensin Aldosterone Syst 7:92–97. doi:10.3317/jraas.2006.015 PubMedGoogle Scholar
  43. 43.
    Hadjadj S et al (2001) Prognostic value of angiotensin-I converting enzyme I/D polymorphism for nephropathy in type 1 diabetes mellitus: a prospective study. J Am Soc Nephrol 12:541–549PubMedGoogle Scholar
  44. 44.
    Curnow KM et al (1995) Alternatively spliced human type 1 angiotensin II receptor mRNAs are translated at different efficiencies and encode two receptor isoforms. Mol Endocrinol 9:1250–1262. doi:10.1210/me.9.9.1250 PubMedGoogle Scholar
  45. 45.
    Bonnardeaux A et al (1994) Angiotensin II type 1 receptor gene polymorphisms in human essential hypertension. Hypertension 24:63–69. http://hyper.ahajournals.org Google Scholar
  46. 46.
    Buraczynska M et al (2002) Association of the renin-angiotensin system gene polymorphism with nephropathy in type II diabetes. Pol Arch Med Wewn 108:725–730PubMedGoogle Scholar
  47. 47.
    Buraczynska M et al (2002) Angiotensin II type 1 receptor gene polymorphism in end-stage renal disease. Nephron 92:51–55. doi:10.1159/000064455 PubMedGoogle Scholar
  48. 48.
    Mogensen CE, Christensen CK (1984) Predicting diabetic nephropathy in insulin-dependent patients. N Engl J Med 311:89–93PubMedGoogle Scholar
  49. 49.
    Kagami S et al (1994) Angiotensin II stimulates extracellular matrix protein synthesis through induction of transforming growth factor-beta expression in rat glomerular mesangial cells. J Clin Invest 93:2431–2437. doi:10.1172/JCI117251 PubMedGoogle Scholar
  50. 50.
    Egger M et al (1997) Language bias in randomised controlled trials published in English and German. Lancet 350:326–329. doi:10.1016/S0140-6736(97)02419-7 PubMedGoogle Scholar
  51. 51.
    Passaro A et al (2003) Effect of metabolic control on homocysteine levels in type 2 diabetic patients: a 3-year follow-up. J Intern Med 254:264–271. doi:10.1046/j.1365-2796.2003.01184.x PubMedGoogle Scholar
  52. 52.
    Ma J et al (1997) Methylenetetrahydrofolate reductase polymorphism, dietary interactions, and risk of colorectal cancer. Cancer Res 57:1098–1102. http://cancerres.aacrjournals.org/content/57/6/1098#related-urls Google Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Wei Ding
    • 1
  • Furu Wang
    • 2
  • Qiaoqiao Fang
    • 3
  • Minmin Zhang
    • 1
  • Jing Chen
    • 1
  • Yong Gu
    • 1
  1. 1.Division of Nephrology, Huashan Hospital and Institute of NephrologyFudan UniversityShanghaiChina
  2. 2.Jiangsu Provincial Center for Disease Prevention and ControlNanjingChina
  3. 3.Department of Respiratory MedicineNanjing Children’s Hospital Affiliated to Nanjing Medical UniversityNanjingChina

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