J Korean Diabetes Assoc.  2007 Mar;31(2):144-150. 10.4093/jkda.2007.31.2.144.

Transforming Growth Factor-beta 1 Gene Polymorphisms According to Diabetic Nephropathy in Type 2 Diabetes

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

Abstract

BACKGROUND: Transforming growth factor-beta is known to play a role in the interaction between metabolic and hemodynamic factors in mediating accumulation of extracellular matrix in the diabetic nephropathy. TGF-beta1 gene polymorphism was associated with circulating TGF-beta levels and influenced the pathogenesis of fibrotic diseases including diabetic nephropathy. In this study, we examined the relationship between TGF-beta1 gene codon 10 polymorphism and type 2 diabetic nephropathy with more than 10-year history of disease.
METHODS
We conducted a case-control study, which enrolled 325 type 2 diabetes. A total of 176 patients with diabetic nephropathy were compared with 149 patients without diabetic nephropathy. TGF-beta1 codon 10 genotyping was determined using polymerase chain reaction with sequence specific primers method.
RESULTS
Distribution of TGF-beta1 codon 10 genotype in the patients either with nephropathy or without nephropathy is confined to Hardy-Weinberg equilibrium. The patients with nephropathy have higher frequency of TGF-beta1 GA/GG genotypes than the patients without nephropathy [GA/GG:AA = 119 (67.6%) : 57 (32.4%) vs. 80 (53.7%) : 69 (46.3%), P < 0.05]. Among patients with diabetic nephropathy, those with TGF-beta1 GA/GG genotypes had higher serum levels of total cholesterol and LDL-cholesterol.
CONCLUSION
Our results suggest that TGF-beta1 gene codon 10 polymorphism may contribute to the type 2 diabetic nephropathy.

Keyword

Diabetic nephropathy; TGF-beta1 polymorphism; Type 2 diabetes

MeSH Terms

Case-Control Studies
Cholesterol
Codon
Diabetic Nephropathies*
Extracellular Matrix
Genotype
Hemodynamics
Humans
Negotiating
Polymerase Chain Reaction
Transforming Growth Factor beta
Transforming Growth Factor beta1
Cholesterol
Codon
Transforming Growth Factor beta
Transforming Growth Factor beta1

Reference

1. Marks JB, Raskin P. Nephropathy and hypertension in diabetes. Med Clin North Am. 1998. 82:877–907.
2. Ritz E, Keller C, Bergis K, Strojek K. Pathogenesis and course of renal disease in IDDM/NIDDM differences and similarities. Am J Hypertens. 1997. 10:S202–S207.
3. Nelson RG, Newman JM, Knwoler WC. Incidence of end stage renal failure in type 2 diabetes mellitus in Pima Indians. Diabeteologia. 1988. 31:730–736.
6. Hostetter TH. Hyperfiltration and glomerulosclerosis. Semin Nephrol. 2003. 23:194–199.
7. Ruggeneti P, Schieppati A, Remuzzi G. Progression, remission, regression of chronic renal disease. Lancet. 2001. 357:1601–1608.
8. Susztak K, Sharma K, Schiffer M, McCue P, Ciccone E, Bttinger EP. Genomic strategies for diabetic nephropathy. J Am Soc Nephrol. 2003. 14:S271–S278.
9. Seaquist ER, Goetz FC, Rich S, Barbosa J. Familial clustering of diabetic kidney disease. Evidence for genetic susceptibility to diabetic nephropathy. N Engl Medi. 1989. 320:1161–1165.
10. Quinn M, Angelico MC, Warram JH, Krolewski AS. Familial factors determine the development of diabetic nephropathy in patients with IDDM. Diabetologia. 1996. 39:940–945.
11. Wolf G. New insights into the pathophysiology of diabetic nephropathy: from haemodynamics to molecular pathology. Eur J Clin Invest. 2004. 34:785–796.
12. Hoffmann BB, Sharma K, Zhu Y, Ziyadeh FN. Transcriptional activation of transforming growth factror-1 in mesangial cell culture by high glucose concentration. Kidney. 1998. 58:1107–1116.
13. Sharma K, Jin Y, Guo J. Neutralization of TGF- by anti-TGF-antibody attenuateskidney hypertrophy and the enhanced extracellular matrix gene expression in STZ-induced diabetic mice. Diabetes. 1995. 44:1139–1146.
14. Gewaltig J, Mangasser-Stephan K, Gartung C. Association of polymorphisms of the transforming growth factor-beta 1 gene with the rate of progression of HCV-induced liver fibrosis. Clin Chim Act. 2002. 316:83–94.
15. Pociot F, Hansen PM, Karlsen AE, Langdahl BL, Johannesen J, Nerup J. TGF-1 Gene mutations in insulin-dependent diabetes mellitus and diabetic nephropathy. J Am Soc Nephrol. 1998. 9:2302–2307.
16. Patel A, Scott WR, Lympany PA, Rippin JD, Gill GV, et al. The TGF-beta 1 gene codon 10 polymorphism contributes to the genetic predisposition to nephropathy in Type 1 diabetes. Diabet Med. 2005. 22:69–73.
17. Teresa YHW, Peter P, Kai MC, Cheuk CS, Man KC, Philp KT. Association of transforming growth factor beta T869C gene polymorphisms with type 2 diabetic nephropathy in Chinese. Kidney Int. 2003. 63:1831–1835.
18. Ellis D, Forrest KY, Erbey J, Orchard TJ. Urinary measurement of transforming growth factor- and type IV collagen as new markers of renal injury: application in diabetic nephropathy. Clin Chem. 1998. 44:950–956.
19. Sharma K, Ziyadeh FN, Alzahabi B, McGowan TA, Kapoor S, Kurnick BR, Kurnik PB, Weisberg LS. Increased renal production of transforming growth factor-1 in patients with type II diabetes. Diabetes. 1997. 46:854–859.
20. Lympany PA, Avila JJ, Mullighan C, Marshall S, Welsh KI, du Bois RM. Rapid genotyping of transforming growth factor beta1 gene polymorphisms in a UK Caucasoid control population using the polymerase chain reaction and sequence-specific primers. Tissue Antigens. 1998. 52:573–578.
21. Akai Y, Sato H, Ozaki H. Association of transforming growth factor-β T29C polymorphism with the progression of diabetic nephropathy. Am J Kidney Dis. 2001. 38:Suppl 1. S182–S185.
22. Wood NAP, Thomson SC, Smith RM. Identification of human TGF-1 signal (leader) sequence polymorphisms by PCR-RFLP. J Immun Methods. 2000. 234:117–122.
23. Li B, Khanna A, Sharma V. TGF-1 DNA polymorphisms, protein levels and blood pressure. Hypertension. 1999. 33:271–275.
24. Yamada Y, Miyauchi A, Takagi Y. Association of the C509-T polymorphism, alone of in combination with the T869-C polymorphsim, of the transforming growth factor beta-1 gene with bone mineral density and genetic susceptibility to osteoporosis in Japanese women. J Mod Med. 2001. 79:149–156.
25. Grainger DJ, Kemp PR, Metcalfe JC, Liu AC, Lawn RM, Williams NR, Schofield PM, Chauhan A. The serum concentration of active transforming growth factor-beta is severely depressed in advanced atherosclerosis. Nat Med. 1999. 1:22–23.
26. Wang XL, Liu SX, Wilcken DE. Circulating transforming growth factor beta 1 and coronary artery disease. Cardiovasc Res. 1997. 34(2):404–410.
27. Sie MP, Uitterlinden AG, Bos MJ, Arp PP, Breteler MM, Koudstaal PJ, Pols HA, Hofman A, van Duijn CM, Witteman JC. TGF-beta 1 polymorphisms and risk of myocardial infarction and stroke: the Rotterdam Study. Stroke. 2006. 37(11):2667–2671.
28. Kim Y, Lee C. The gene encoding transforming growth factor beta 1 confers risk of ischemic stroke and vascular dementia. Stroke. 2006. 37(11):2843–2845.
29. Yokota M, Ichihara S, Lin TL, Nakashima N, Yamada Y. Association of a T29 224C polymorphism of the transforming growth factor-1 gene with genetic susceptibility to myocardial infarction in Japanese. Circulation. 2000. 101:2783–2787.
30. Matsuda T, Yamamoto T, Muraguchi A, Saatcioglu F. Cross-talk between transforming growth factor-beta and estrogen receptor signaling through Smad3. J Biol Chem. 2001. 276(46):42908–42914.
31. Beranek M, Kankova K, Benes P, Izakovicova-Holla L, Znojil V, Hajek D, Vlkova E, Vacha J. Polymorphism R25P in the gene encoding transforming growth factor-beta (TGF-beta1) is a newly identified risk factor for proliferative diabetic retinopathy. Am J Med Genet. 2002. 109(4):278–283.
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