Seminars in Nephrology
Volume 30, Issue 4 , Pages 418-425 , July 2010

Gene Polymorphisms in Renal Transplantation

  • Monica Grafals, MD

      Affiliations

    • Division of Transplantation, Lahey Clinic, Tufts University, Burlington, MA
    • Corresponding Author InformationAddress reprint requests to Monica Grafals, MD, Assistant Professor, Division of Transplantation, Lahey Clinic Transplant Center, 41 Mall Rd, Burlington, MA 01805
    • ,
  • Leila Kamal, MD

      Affiliations

    • Internal Medicine Department, Staten Hospitals, Staten Island, NY
    • ,
  • Daniel Chung, BA

      Affiliations

    • Transplant Research Center, Harvard Medical School, Boston, MA
    • ,
  • Reza Abdi, MD

      Affiliations

    • Transplant Research Center, Division of Nephrology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA

References 

  1. Li C, Yang CW. The pathogenesis and treatment of chronic allograft nephropathy. Nat Rev Nephrol. 2009;5:513–519
  2. Paul LC. Chronic allograft nephropathy: an update. Kidney Int. 1999;56:783–793
  3. Hutchinson IV. The role of transforming growth factor-beta in transplant rejection. Transplant Proc. 1999;31:9S–13S
  4. Campistol JM, et al. Role of transforming growth factor-beta1 in the progression of chronic allograft nephropathy. Nephrol Dial Transplant. 2001;16(Suppl 1):114–116
  5. Minguela A, et al. Implication of Th1, Th2, and Th3 cytokines in liver graft acceptance. Transplant Proc. 1999;31:519–520
  6. Viklicky O, et al. TGF-beta1 expression and chronic allograft nephropathy in protocol kidney graft biopsy. Physiol Res. 2003;52:353–360
  7. Miossec P. IL-17 and Th17 cells in human inflammatory diseases. Microbes Infect. 2009;11:625–630
  8. Yuan X, et al. Targeting Tim-1 to overcome resistance to transplantation tolerance mediated by CD8 T17 cells. Proc Natl Acad Sci U S A. 2009;106:10734–10739
  9. Border WA, Noble NA. Transforming growth factor beta in tissue fibrosis. N Engl J Med. 1994;331:1286–1292
  10. Gellai M. Physiological role of endothelin in cardiovascular and renal hemodynamics: studies in animals. Curr Opin Nephrol Hypertens. 1997;6:64–68
  11. Gellai M, et al. Contribution of endogenous endothelin-1 to the maintenance of vascular tone: role of nitric oxide. Pharmacology. 1997;55:299–308
  12. Perrella MA, et al. Suppression of interleukin-1beta-induced nitric-oxide synthase promoter/enhancer activity by transforming growth factor-beta1 in vascular smooth muscle cells (Evidence for mechanisms other than NF-kappaB). J Biol Chem. 1996;271:13776–13780
  13. Ahuja SS, et al. Regulation of transforming growth factor-beta 1 and its receptor by cyclosporine in human T lymphocytes. Transplantation. 1995;60:718–723
  14. Khanna A, et al. In vivo hyperexpression of transforming growth factor-beta1 in mice: stimulation by cyclosporine. Transplantation. 1997;63:1037–1039
  15. Wolf G, et al. Transforming growth factor beta mediates the angiotensin-II-induced stimulation of collagen type IV synthesis in cultured murine proximal tubular cells. Nephrol Dial Transplant. 1996;11:263–269
  16. Shin GT, et al. In vivo expression of transforming growth factor-beta1 in humans: stimulation by cyclosporine. Transplantation. 1998;65:313–318
  17. Cuhaci B, et al. Transforming growth factor-beta levels in human allograft chronic fibrosis correlate with rate of decline in renal function. Transplantation. 1999;68:785–790
  18. Randall LL, Hardy SJ. Unity in function in the absence of consensus in sequence: role of leader peptides in export. Science. 1989;243:1156–1159
  19. Benson SA, Hall MN, Silhavy TJ. Genetic analysis of protein export in Escherichia coli K12. Annu Rev Biochem. 1985;54:101–134
  20. Lyons RM, et al. Mechanism of activation of latent recombinant transforming growth factor beta 1 by plasmin. J Cell Biol. 1990;110:1361–1367
  21. Hueso M, et al. Relationship between subclinical rejection and genotype, renal messenger RNA, and plasma protein transforming growth factor-beta1 levels. Transplantation. 2006;81:1463–1466
  22. Awad MR, et al. Genotypic variation in the transforming growth factor-beta1 gene: association with transforming growth factor-beta1 production, fibrotic lung disease, and graft fibrosis after lung transplantation. Transplantation. 1998;66:1014–1020
  23. Yamada Y, et al. Association of a polymorphism of the transforming growth factor-beta1 gene with genetic susceptibility to osteoporosis in postmenopausal Japanese women. J Bone Miner Res. 1998;13:1569–1576
  24. Thakkinstian A, et al. Association between cytokine gene polymorphisms and outcomes in renal transplantation: a meta-analysis of individual patient data. Nephrol Dial Transplant. 2008;23:3017–3023
  25. Chow KM, et al. Transforming growth factor-beta1 gene polymorphism in renal transplant recipients. Ren Fail. 2005;27:671–675
  26. Inigo P, et al. [Role of transforming growth factor beta-1 gene polymorphisms in the development of chronic allograft nephropathy in renal transplant recipients]. Nefrologia. 2003;23:312–320
  27. Nikolova PN, et al. Cytokine gene polymorphism in kidney transplantation—impact of TGF-beta 1, TNF-alpha and IL-6 on graft outcome. Transpl Immunol. 2008;18:344–348
  28. van de Wetering J, et al. The impact of transforming growth factor-beta1 gene polymorphism on end-stage renal failure after heart transplantation. Transplantation. 2006;82:1744–1748
  29. Cheng ZJ, Vapaatalo H, Mervaala E. Angiotensin II and vascular inflammation. Med Sci Monit. 2005;11:RA194–RA205
  30. Suzuki Y, et al. Inflammation and angiotensin II. Int J Biochem Cell Biol. 2003;356:881–900
  31. Geara AS, et al. The renin-angiotensin system: an old, newly discovered player in immunoregulation. Transplant Rev (Orlando). 2009;23:151–158
  32. Cruzado JM, et al. Influence of nephron mass in development of chronic renal failure after prolonged warm renal ischemia. Am J Physiol Renal Physiol. 2000;279:F259–F269
  33. Mackenzie HS, et al. Nephron supply is a major determinant of long-term renal allograft outcome in rats. J Clin Invest. 1994;94:2148–2152
  34. Meyer TW, et al. Reversing glomerular hypertension stabilizes established glomerular injury in renal ablation. J Hypertens Suppl. 1986;4:S239–S241
  35. Amuchastegui SC, et al. Chronic allograft nephropathy in the rat is improved by angiotensin II receptor blockade but not by calcium channel antagonism. J Am Soc Nephrol. 1998;9:1948–1955
  36. Lutz J, et al. Angiotensin type 1 and type 2 receptor blockade in chronic allograft nephropathy. Kidney Int. 2006;70:1080–1088
  37. Noris M, et al. ACE inhibition limits chronic injury of kidney transplant even with treatment started when lesions are established. Kidney Int. 2003;64:2253–2261
  38. Noble NA, Border WA. Angiotensin II in renal fibrosis: should TGF-beta rather than blood pressure be the therapeutic target?. Semin Nephrol. 1997;17:455–466
  39. Border WA, Noble NA. Interactions of transforming growth factor-beta and angiotensin II in renal fibrosis. Hypertension. 1998;31:181–188
  40. Wolf G, et al. Angiotensin II-stimulated expression of transforming growth factor beta in renal proximal tubular cells: attenuation after stable transfection with the c-mas oncogene. Kidney Int. 1995;48:1818–1827
  41. Wolf G, et al. Angiotensin II-induced hypertrophy of cultured murine proximal tubular cells is mediated by endogenous transforming growth factor-beta. J Clin Invest. 1993;92:1366–1372
  42. Gibbons GH, Pratt RE, Dzau VJ. Vascular smooth muscle cell hypertrophy vs. hyperplasia (Autocrine transforming growth factor-beta 1 expression determines growth response to angiotensin II). J Clin Invest. 1992;90:456–461
  43. Brezniceanu ML, et al. Transforming growth factor-beta 1 stimulates angiotensinogen gene expression in kidney proximal tubular cells. Kidney Int. 2006;69:1977–1985
  44. Rigat B, et al. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest. 1990;86:1343–1346
  45. Agachan B, et al. Angiotensin converting enzyme I/D, angiotensinogen T174M-M235T and angiotensin II type 1 receptor A1166C gene polymorphisms in Turkish hypertensive patients. Exp Mol Med. 2003;35:545–549
  46. Jiang X, et al. Association between renin-angiotensin system gene polymorphism and essential hypertension: a community-based study. J Hum Hypertens. 2009;23:176–181
  47. Abdi R, et al. Angiotensin gene polymorphism as a determinant of posttransplantation renal dysfunction and hypertension. Transplantation. 2001;72:726–729
  48. Barocci S, et al. Correlation between angiotensin-converting enzyme gene insertion/deletion polymorphism and kidney graft long-term outcome in pediatric recipients: a single-center analysis. Transplantation. 1999;67:534–538
  49. Rodriguez-Moreno A, et al. Association of the genetic polymorphisms of the renin-angiotensin system with kidney graft long-term outcome: preliminary results. Transplant Proc. 2005;37:3716–3717
  50. Beige J, et al. Angiotensin-converting-enzyme insertion/deletion genotype and long-term renal allograft survival. Nephrol Dial Transplant. 1998;13:735–738
  51. Biselli PM, et al. Angiotensin-converting enzyme gene polymorphism in chronic allograft nephropathy. Transplant Proc. 2006;38:1327–1328
  52. Broekroelofs J, et al. Risk factors for long-term renal survival after renal transplantation: a role for angiotensin-converting enzyme (insertion/deletion) polymorphism?. J Am Soc Nephrol. 1998;9:2075–2081
  53. Harden PN, et al. Polymorphisms in angiotensin-converting-enzyme gene and progression of IgA nephropathy. Lancet. 1995;345:1540–1542
  54. Waller JR, Nicholson ML. Molecular mechanisms of renal allograft fibrosis. Br J Surg. 2001;88:1429–1441
  55. Chang HR, et al. Relationships between circulating matrix metalloproteinase-2 and -9 and renal function in patients with chronic kidney disease. Clin Chim Acta. 2006;366:243–248
  56. Inkinen KA, et al. Fibrosis and matrix metalloproteinases in rat renal allografts. Transpl Int. 2005;18:506–512
  57. Lutz J, et al. Inhibition of matrix metalloproteinases during chronic allograft nephropathy in rats. Transplantation. 2005;79:655–661
  58. Mas V, et al. Establishing the molecular pathways involved in chronic allograft nephropathy for testing new noninvasive diagnostic markers. Transplantation. 2007;83:448–457
  59. Rodrigo E, et al. Circulating levels of matrix metalloproteinases MMP-3 and MMP-2 in renal transplant recipients with chronic transplant nephropathy. Nephrol Dial Transplant. 2000;15:2041–2045
  60. Rodder S, et al. Renal allografts with IF/TA display distinct expression profiles of metzincins and related genes. Am J Transplant. 2009;9:517–526
  61. Nicholson ML, Waller JR, Bicknell GR. Renal transplant fibrosis correlates with intragraft expression of tissue inhibitor of metalloproteinase messenger RNA. Br J Surg. 2002;89:933–937
  62. Cozzolino M, et al. Matrix metalloproteinase-1 and matrix metalloproteinase-3 gene promoter polymorphisms are associated with mortality in haemodialysis patients. Nephrol Dial Transplant. 2009;24:2207–2212
  63. Hirakawa S, et al. Evaluation of genetic variation and association in the matrix metalloproteinase 9 (MMP9) gene in ESRD patients. Am J Kidney Dis. 2003;42:133–142
  64. Nair S, et al. Further evidence for the association of MMP9 with nephropathy in type 2 diabetes and application of DNA pooling technology to candidate gene screening. J Nephrol. 2008;21:400–405
  65. Ye S. Polymorphism in matrix metalloproteinase gene promoters: implication in regulation of gene expression and susceptibility of various diseases. Matrix Biol. 2000;19:623–629
  66. Cho JH, et al. Association of C-509T and T869C polymorphisms of transforming growth factor-beta1 gene with chronic allograft nephropathy and graft survival in Korean renal transplant recipients. Transplant Proc. 2008;40:2355–2360
  67. Melk A, et al. Cytokine single nucleotide polymorphisms and intrarenal gene expression in chronic allograft nephropathy in children. Kidney Int. 2003;64:314–320
  68. Dmitrienko S, et al. Immune response gene polymorphisms in renal transplant recipients. Transplantation. 2005;80:1773–1782
  69. Alakulppi NS, et al. Cytokine gene polymorphisms and risks of acute rejection and delayed graft function after kidney transplantation. Transplantation. 2004;78:1422–1428
  70. Park JY, et al. TNF-alpha and TGF-beta1 gene polymorphisms and renal allograft rejection in Koreans. Tissue Antigens. 2004;64:660–666
  71. Akcay A, et al. Angiotensin-converting enzyme genotype is a predictive factor in the peak panel-reactive antibody response. Transplant Proc. 2004;36:35–37
  72. Reis K, et al. Angiotensinogen and plasminogen activator inhibitor-1 gene polymorphism in relation to chronic allograft dysfunction. Clin Transplant. 2005;19:10–14
  73. Hueso M, et al. Angiotensin converting enzyme genotype and chronic allograft nephropathy in protocol biopsies. J Am Soc Nephrol. 2004;15:2229–2236
  74. Prasad GV, et al. Angiotensinogen M235T genotype predicts progression in chronic renal allograft dysfunction. Transplantation. 2003;75:209–216

PII: S0270-9295(10)00100-2

doi: 10.1016/j.semnephrol.2010.06.008

Seminars in Nephrology
Volume 30, Issue 4 , Pages 418-425 , July 2010

Article Tools