Journal List > J Korean Diabetes Assoc > v.31(2) > 1062428

Jeon, Kim, Ho, Kwon, and Oh: Transforming Growth Factor-beta 1 Gene Polymorphisms According to Diabetic Nephropathy in Type 2 Diabetes

Abstract

Background

Transforming growth factor-β 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-β1 gene polymorphism was associated with circulating TGF-β levels and influenced the pathogenesis of fibrotic diseases including diabetic nephropathy.
In this study, we examined the relationship between TGF-β1 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-β1 codon 10 genotyping was determined using polymerase chain reaction with sequence specific primers method.

Results

Distribution of TGF-β1 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-β1 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-β1 GA/GG genotypes had higher serum levels of total cholesterol and LDL-cholesterol.

Conclusion

Our results suggest that TGF-β1 gene codon 10 polymorphism may contribute to the type 2 diabetic nephropathy.

Figures and Tables

Table 1
Clinical characteristics of patients with Type 2 diabetes with or without diabetic nephropathy
jkda-31-144-i001

Data are means ± SD or %.

BMI, body mass index; DBP, diastolic blood pressure; FBS, fasting blood sugar; HDL, high density lipoprotein; LDL, low density lipoprotein; PP2, 2 hours postprandial blood sugar; SBP, systolic blood pressure.

Table 2
Distributions of TGF-β1 genotypes and alleles in patients with or without diabetic nephropathy
jkda-31-144-i002
Table 3
Clinical characteristics of different TGF-β1 genotypes in diabetic nephropathy
jkda-31-144-i003
Table 4
TGF-β1 genotype in diabetic nephropathy according to severity of diabetic nephropathy
jkda-31-144-i004
Table 5
TGF-β1 genotype according to micro and macrovascular complications
jkda-31-144-i005

References

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.
TOOLS
Similar articles