Korean Diabetes J.  2008 Oct;32(5):402-408. 10.4093/kdj.2008.32.5.402.

Association Study of the Peroxisome Proliferators-Activated Receptor gamma2 Pro12Ala Polymorphism with Diabetic Nephropathy

Affiliations
  • 1Department of Internal Medicine, Chungbuk National University College of Medicine, Korea.

Abstract

BACKGROUND: Peroxisome proliferators-activated receptor gamma (PPARgamma) is a member of the nuclear hormone receptor superfamily of ligand-activated transcription factors and known to play a role in regulating the expression of numerous genes involved in lipid metabolism, metabolic syndrome, inflammation, and atherosclerosis. The PPARgamma2 Pro12Ala polymorphism has recently been shown to be associated with diabetic nephropathy. In this study, we evaluated the relationship between PPARgamma2 Pro12Ala polymorphism and type 2 diabetic nephropathy whose duration of diabetes was over 10 years.
METHODS
We conducted a case-control study, which enrolled 367 patients with type 2 diabetes. Genotyping of PPARgamma2 Pro12Ala polymorphism was performed using polymerase chain reaction followed by digestion with Hae III restriction enzyme.
RESULTS
The genotype or allele frequencies of PPARgamma2 Pro12Ala polymorphism were not significantly different in diabetic patients with or without diabetic nephropathy. The genotype frequencies in terms of diabetic retinopathy and macrovascular complications such as coronary artery disease or stroke were not different either. Interestingly, nephropathy patients with Ala/Pro genotype showed lower C-peptide levels than those of Pro/Pro genotype.
CONCLUSION
Our results suggest that PPARgamma2 Pro12Ala polymorphism is not associated with diabetic nephropathy in type 2 diabetic patients.

Keyword

Diabetic nephropathy; PPARgamma2 Pro12Ala polymorphism; Type 2 diabetes

MeSH Terms

Atherosclerosis
C-Peptide
Case-Control Studies
Coronary Artery Disease
Diabetic Nephropathies
Diabetic Retinopathy
Digestion
Gene Frequency
Genotype
Humans
Inflammation
Lipid Metabolism
Peroxisomes
Polymerase Chain Reaction
PPAR gamma
Stroke
Transcription Factors
C-Peptide
PPAR gamma
Transcription Factors

Figure

  • Fig. 1 Genotyping of PPAR-γ2 gene. The amplified PCR products were digested with the restriction enzyme Hae III. The Pro12 alleles gives one 132-and 22-bp fragments whereas the Ala12 alleles gives one 155-bp fragment. Lane 1,3,5,6,7,8: Pro/Pro genotype, Lane 2, 4: Ala/Pro genotype.


Reference

1. Desvergne B, Wahli W. Peroxisome proliferators activated receptors; Nuclear control of metabolism. Endocr Rev. 1999. 20:649–688.
2. Rosen ED, Spiegelman BM. PPARgamma: A nuclear regulator of metabolism, differentiation, and cell growth. J Biol Chem. 2001. 276:37731–37734.
3. Lehmann JM, Moore LB, Smith-Oliver TA, Wilkinson WO, Wilson TM, Kliewer SA. An antidabetic thiazolidione is high affinity ligand for peroxisome proliferators-activated receptor (PPAR). J Biol Chem. 1995. 270:12953–12956.
4. Mancini FP, Vaccaro O, Sabatino L, Tufano A, Rivellese AA, Riccardi G, Colantuoni V. Pro12Ala substitution in the peroxisome proliferators-activated receptor-2 is not associated with type 2 diabetes. Diabetes. 1999. 48:1466–1468.
5. Ringel J, Engeli S, Distler A, Sharma AM. Pro12Ala missense mutation of the peroxisome proliferators-activated receptor and DM. Biocheml Biophys Res Commun. 1999. 254:450–453.
6. Clement K, Hercberg S, Passinge B, Galan P, Varroud-Vial M, Shuldiner AR, Beamer BA, Charpentier G, Guy-Grand B, Froguel P, Vaisse C. The Pro115Gln and pro12Ala PPAR gene mutations in obesity and type 2 diabetes. Intl J Obes Relat Metab Disord. 2000. 24:391–393.
7. Mohazzab KM, Kaminski PM, Wolin MS. NADH oxidoreductase is a major source of superoxide anion in bovine coronary artery endothelium. Am J Physiol. 1994. 266:H2568–H2572.
8. Groemping Y, Rittinger K. Activation and assembly of the NADPH oxidase: A structural perspective. Biochem J. 2005. 386:401–416.
9. Calkin AC, Giunti S, Jandeleit-Dahm KA, Allen TJ, Cooper ME, Thomas MC. PPAR-alpha and -gamma agonists attenuate diabetic kidney disease in the apolipoprotein E knockout mouse. Nephrol Dial Transplant. 2006. 21:2399–2405.
10. Ma J, Marcantoni C, Linton MF, Fazio S, Fogo AB. Peroxisome proliferator-activated receptor-gamma agonist troglitazone protects agonist nondiabetic glomerulosclerosis in rats. Kidney Int. 2001. 59:1899–1910.
11. Sarafidis PA, Bakris GL. Protection of the kidney by thiazolidinediones: an assessment from bench to bedside. Kidney Int. 2006. 70:1223–1233.
12. Izzedine H, Launay-Vacher V, Buhaescu I, Heurtier A, Baumelou A, Deray G. PPAR-gamma-agonists renal effects. Minerva Urol Nefol. 2005. 57:247–260.
13. Deeb SS, Fajas L, Nemoto M, Pihlajamäki J, Mykkänen L, Kuusisto J, Laakso M, Fujimoto W, Auwerx J. A Pro12Ala substitution in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity. Nat Genet. 1998. 20:284–287.
14. Herrmann SM, Ringel J, Wang JG, Staessen JA, Brand E. Peroxisome proliferator-activated receptor-γ2 polymorphism Pro12Ala is associated with nephropathy in type 2 diabetes. Diabetes. 2002. 51:2653–2657.
15. Caramori ML, Canari LH, Costa LA, Gross JL. The human Peroxisome proliferator-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.
16. 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.
17. Moon MK, Cho YM, Jung HS, Park YJ, Yoon KH, Sung YA, Park BL, Lee HK, Park KS, Shin HD. Genetic polymorphisms in peroxisome proliferator-activated receptor gamma are associated with Type 2 diabetes mellitus and obesity in the Korean population. Diabet Med. 2005. 22:1161–1166.
18. Yamamoto J, Kageyama S, Nemoto M, Sasaki T, Sakurai T, Ishibashi K, Mimura A, Yokota K, Tajima N. PPARgamma2 pro12Ala polymorphism and insulin resistance in Japanese hypertensive patients. Hypertens Res. 2002. 25:25–29.
19. Oh EY, Min KM, Chung JH, Min YK, Lee MS, Kim KW, LEE MK. Significance of pro12ala mutation in peroxisome proliferator-activated receptor-γ2 in Korean diabetic and obese subjects. J Clin Endoclinol Metab. 2000. 85:1801–1804.
20. Oh SJ, Kang SY, Kim DY, Kim YS, Yang IM, Paeng JR. Polymorphisms of PPARγ2 gene in patients with type 2 diabetes mellitus and obesity. Korean J Med. 2000. 59:132–141.
21. Pollex RL, Mamakeesick M, Zinman B, Harris SB, Hegele RA, Hanley AJ. Peroxisome proliferator-activated receptor gamma polymorphism Pro12Ala is associated with nephropathy in type 2 diabetes. J Diabetes Complications. 2007. 21:166–171.
Full Text Links
  • KDJ
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr