Skip to main content
The Egyptian Journal of Internal Medicine
Download PDF

The association between diabetic nephropathy and polymorphisms in PPARγ Pro 12Ala and CCR5δ 32 genes in type 2 diabetes

The Egyptian Journal of Internal Medicine volume 25, pages 10–14 (2013)Cite this article

Abstract

Background

Diabetic nephropathy is one of the debilitating complications of type 2 diabetes and the leading cause for end-stage renal disease requiring renal replacement therapy. Currently identified risk factors do not fully explain the susceptibility of some patients to diabetic nephropathy. Peroxisome proliferator-activated receptor γ (PPARγ) Pro12Ala gene polymorphisms modulate insulin sensitivity and oxidative stress in diabetic patients, and conflicting data exist on its association with kidney disease in diabetes. Several polymorphisms in another immune modulator set of genes, the C–C chemokine receptor 5 (CCR5) genes, were associated with diabetic nephropathy. However, CCR5δ 32 gene polymorphisms were not studied in patients with diabetic nephropathy. The aim of this study was to assess the association between polymorphisms in both PPARγ Pro12Ala and CCR5δ 32 genes and the presence of diabetic nephropathy in Egyptian patients with type 2 diabetes.

Methods

We included 51 patients having type 2 diabetes for at least 5 years. They were all normotensive patients selected from the outpatient clinic with no other clinically identifiable risk factor for kidney disease. Genotype detection for PPARγ Pro12Ala and CCR5δ 32 gene polymorphisms was carried out using the PCR technique. Clinical data, HbA1c levels, lipid profile, and fasting and postprandial blood sugar levels were recorded. Serum creatinine levels and the urinary albumin/creatinine ratio were measured to stratify the participants according to the presence or absence of diabetic nephropathy.

Results

Age, sex, BMI, HbA1c, and duration of diabetes were not significantly different among patients with and those without diabetic nephropathy. Diabetic nephropathy patients had a significantly higher urinary albumin/creatinine ratio and lower estimated glomerular filtration rate levels (P < 0.0001). Homozygotes for the PPARγ Pro12Ala Pro–Pro allele constituted 82% of our total study population and 86.4% of patients with diabetic nephropathy; the remaining were Pro–Ala heterozygotes, and we had no Ala–Ala homozygotes. The odds ratio for diabetic nephropathy in Pro–Pro homozygotes was 3.5 (P= 0.075, 95% confidence interval, 0.8–15). The Pro allele was present in 75% of patients with nephropathy and 50% of those without nephropathy. The Pro allele was significantly associated with diabetic nephropathy compared with the Ala allele (odds ratio = 3.5, P=0.012, 95% confidence interval, 1.3–15). With regard to the CCR5δ 32 insertion/deletion genotype, 24 patients were homozygous for the insertion polymorphism, two were homozygous for the deletion polymorphism, and the remaining 25 were insertion/deletion heterozygotes. There was no significant difference between nephropathic and non-nephropathic patients as regards the CCR5δ 32 genotype (P=0.3) or the frequency of allele distribution (P = 0.6).

Conclusion

The Pro allele of PPARγ Pro12Ala was associated with diabetic nephropathy. Polymorphisms in the CCR5δ 32 gene did not show an association with diabetic nephropathy.

References

  1. American Diabetes Association. All about Diabetes. Diabetes Care 2004; 27:S1–S78.

    Article  Google Scholar 

  2. American Diabetes Association. Position statement. Diabetes Care 2004; 27:S79–S83.

    Article  Google Scholar 

  3. Caramori ML, Kim Y, Huang C, Fish AJ, Rich SS, Miller ME, et al. Cellular basis of diabetic nephropathy: I. Study design and structural functional relationships in patients with long standing type I diabetes. Diabetes 2002; 51:506–513.

    Article  CAS  Google Scholar 

  4. Yu R, Bo H, Huang S. Association between the PPARG gene polymorphism and the risk of diabetic nephropathy: a meta-analysis. Genet Test Mol Biomarkers 2012; 16:429–434.

    Article  CAS  Google Scholar 

  5. Erdogan M, Karadeniz M, Eroglu Z, Tezcanli B, Selvi N, Yilmaz C. The relationship of the peroxisome proliferator-activated receptor-gamma 2 exon 2 and exon 6 gene polymorphism in Turkish type II diabetic patients with and without nephropathy. Diabetes Res Clin Pract 2007; 78:355–359.

    Article  CAS  Google Scholar 

  6. Ruster C, Wolf G. The role of chemokines and chemokine receptors in diabetic nephropathy. Front Biosci 2008; 13:944–955.

    Article  CAS  Google Scholar 

  7. Huang C, Kim Y, Caramori ML, Fish AJ, Rich SS, Miller ME, et al. Cellular basis of diabetic nephropathy: II. The transforming growth factor beta system and diabetic nephropathy lesions in type I diabetes. Diabetes. 51; 2002. pp. 3577–3581.

    Article  CAS  Google Scholar 

  8. Krolewski AS. Genetics of diabetic nephropathy: evidence for major and minor gene effects. Kidney Int 1999; 55:1582–1596.

    Article  CAS  Google Scholar 

  9. Jorsal A, Tarnow L, Lajer M, Ek J, Hansen T, Pedersen O, Parving HH. The PPAR gamma 2 Pro12Ala variant predicts ESRD and mortality in patients with type 1 diabetes and diabetic nephropathy. Mol Genet Metab 2008; 94:347–351.

    Article  CAS  Google Scholar 

  10. Liu L, Zheng T, Wang F, Wang N, Song Y, Li M, et al. Pro12Ala polymorphism in the PPARG gene contributes to the development of diabetic nephropathy in Chinese type 2 diabetic patients. Diabetes Care 2010; 33:144–149.

    Article  CAS  Google Scholar 

  11. Gambelunghe G, Ghaderi M, Brozzetti A, Del Sindaco P, Gharizadeh B, Nyren P, et al. Lack of association of CCR2-64I and CCR5-Delta 32 with type 1 diabetes and latent autoimmune diabetes in adults. Hum Immunol 2003; 64:629–632.

    Article  CAS  Google Scholar 

  12. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 18:499–502.

    Article  CAS  Google Scholar 

  13. Levy AS. A simplified equation to predict glomerular filtration rate from serum creatinine. Ann Intern Med 1999; 130:461–470.

    Article  Google Scholar 

  14. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988; 16:1215–1221.

    Article  CAS  Google Scholar 

  15. Lindner E, Nordang G, Melum E, et al. Lack of association between the chemokine receptor 5 polymorphism CCR5delta32 in rheumatoid arthritis and juvenile idiopathic arthritis. BMC Med Genet 2007; 8:33.

    Article  Google Scholar 

  16. Hamann A, Munzberg H, Buttron P, et al. Missense variants in the human peroxisome proliferator-activated receptor-g2 gene in lean and obese subjects. Eur J Endocrinol 1999; 141:90–92.

    Article  CAS  Google Scholar 

  17. Caramori ML, Canani LH, Costa LA, et al. The human peroxisome pro-liferator-activated receptor gamma2 (PPARgamma2) Pro12Ala polymorphism is associated with decreased risk of diabetic nephropathy in patients with type 2 diabetes. Diabetes 2003; 52:3010–3013.

    Article  CAS  Google Scholar 

  18. Herrmann SM, Ringel J, Wang JG, et al. Peroxisome proliferator-activated receptor-gamma2 polymorphism Pro12Ala is associated with nephropathy in type 2 diabetes: The Berlin Diabetes Mellitus (BeDiaM) Study. Diabetes 2002; 51:2653–2657.

    Article  CAS  Google Scholar 

  19. Sugawara A, Uruno A, Kudo M, Matsuda K, Yang CW, Ito S. Effects of PPARγ on hypertension, atherosclerosis, and chronic kidney disease. Endocr J 2010; 57:847–852.

    Article  CAS  Google Scholar 

  20. Ichinose K, Kawasaki E, Eguchi K. Recent advancement of understanding pathogenesis of type 1 diabetes and potential relevance to diabetic nephropathy. Am J Nephrol 2007; 27:554–564.

    Article  CAS  Google Scholar 

  21. Su Q, Mai Z, Zang N, Wu S, Xiao X, Liang H. Distribution of CCR5-{delta}32, CCR2-64I, and SDF1-3’A in Guangxi Zhuang population. J Int Assoc Physicians AIDS Care (Chic) 2010; 9:145–149.

    Article  Google Scholar 

  22. Muntinghe FL, Verduijn M, Zuurman MW, Grootendorst DC, Carrero JJ, Qureshi AR, et al. CCR5 deletion protects against inflammation-associated mortality in dialysis patients. J Am Soc Nephrol 2009; 20: 1641–1649.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Clinical Pathology, Cairo University, Cairo, Egypt

    Asmaa I. Ahmed, Noha A. Osman & Manal M. Kamal

  2. Department of Internal Medicine, Kasr Al-Ainy School of Medicine, Cairo University, Cairo, Egypt

    Noha A. Osman & Mohamed M. NasrAllah

Authors
  1. Asmaa I. Ahmed
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Noha A. Osman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mohamed M. NasrAllah
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Manal M. Kamal
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Noha A. Osman.

Rights and permissions

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ahmed, A.I., Osman, N.A., NasrAllah, M.M. et al. The association between diabetic nephropathy and polymorphisms in PPARγ Pro 12Ala and CCR5δ 32 genes in type 2 diabetes. Egypt J Intern Med 25, 10–14 (2013). https://doi.org/10.7123/01.EJIM.0000425954.57680.ee

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.7123/01.EJIM.0000425954.57680.ee

Keywords