Molecular pathophysiology of late diabetic complications – genetic predisposition to the development of diabetic complications

Czech version

Authors: K. Kaňková
Authors‘ workplace: Ústav patologické fyziologie Lékařské fakulty MU, Brno, přednostka prof. MUDr. Anna Vašků, CSc.
Published in: Vnitř Lék 2005; 51(4): 438-449
Category: Reviews

Overview

Our contribution deals with a subject of genetic determination of susceptibility to the development of late diabetic complications, ways and means of its study and potential clinical application of this piece of knowledge for assessing of individual’s risk. Existence of genetic risk factors for diabetic complications is supported by (i) data regarding the relationship between prevalence and incidence of complications on one hand and diabetes duration and compensation on the other, (ii) frequent proof of familiar aggregation and (iii) results of segregation analyses. Aforementioned facts apply almost exclusively to the diabetic nephropathy and macrovascular disease. Pathogenically, functional variability in relevant metabolic and hemodynamic parameters as a result of genetic variability seems to play a role. Genetic component of susceptibility to diabetic complications exhibits, from the point of view of genetics, features of so-called complex disease. We summarise meaningful and the most significant results of linkage and association studies of genetics of diabetic nephropathy and cardiovascular diseases accompanying diabetes in detail.

Key words:
diabetes mellitus – diabetic complications – diabetic nephropathy – association – polymorphism – complex disease

Sources

1. Kaňková K. Molecular pathophysiology of late diabetic complications – hyperglycemia-induced changes. Vnitř Lék 2004; 50: 756–767.

2. Strowig S, Raskin P. Glycemic control and diabetic complications. Diabetes Care 1992; 15: 1126–1140.

3. Barbosa J. Nature and nurture: The genetics of diabetic microangiopathy In: Podolsky S, Viswanathan M (eds). Secondary diabetes. The spectrum of diabetic syndromes. New York: Raven Press 1980.

4. Kaňková K. Role of genetic variability in systems of receptor–mediated and enzymatic defence against glycation in the long–term consequences of diabetes mellitus. Biochem Soc Trans 2003; 31: 1364–1366.

5. Lander ES, Schork NJ. Genetic dissection of complex traits. Science 1994; 265: 2037–2048.

6. Rogus JJ, Warram JH, Krolewski AS. Genetic studies of late diabetic complications: the overlooked importance of diabetes duration before complication onset. Diabetes 2002; 51: 1655–1662.

7. Strauch K, Fimmers R, Baur MP et al. How to model a complex trait. 1. General considerations and suggestions. Hum Hered 2003; 55: 202–210.

8. Glazier AM, Nadeau JH, Aitman TJ. Finding genes that underlie complex traits. Science 2002; 298: 2345– 2349.

9. Ruiz J. Diabetes mellitus and the late complications: influence of the genetic factors. Diabetes Metab 1997; 23(Suppl 2): 57–63.

10. Seaquist ER, Goetz FC, Rich S et al. Familial clustering of diabetic kidney disease. Evidence for genetic susceptibility to diabetic nephropathy. N Engl J Med 1989; 320: 1161–1165.

11. Borch-Johnsen K, Norgaard K, Hommel E et al. Is diabetic nephropathy an inherited complication? Kidney Int 1992; 41: 719–722.

12. Quinn M, Angelico MC, Warram JH et al. Familial factors determine the development of diabetic nephropathy in patients with IDDM. Diabetologia 1996; 39: 940–945.

13 Faronato PP, Maioli M, Tonolo G et al. Clustering of albumin excretion rate abnormalities in Caucasian patients with NIDDM. The Italian NIDDM Nephropathy Study Group. Diabetologia 1997; 40: 816–823.

14. Pettitt DJ, Saad MF, Bennett PH et al. Familial predisposition to renal disease in two generations of Pima Indians with type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 1990; 33: 438–443.

15. Canani LH, Gerchman F, Gross JL. Familial clustering of diabetic nephropathy in Brazilian type 2 diabetic patients. Diabetes 1999; 48: 909–913.

16. Freedman BI, Tuttle AB, Spray BJ. Familial predisposition to nephropathy in African–Americans with non–insulin–dependent diabetes mellitus. Am J Kidney Dis 1995; 25: 710–713.

17. Clustering of long–term complications in families with diabetes in the diabetes control and complications trial. The Diabetes Control and Complications Trial Research Group. Diabetes 1997; 46: 1829–1839.

18. Krolewski AS, Warram JH, Christlieb AR et al. The changing natural history of nephropathy in type I diabetes. Am J Med 1985; 78: 785–794.

19. Imperatore G, Knowler WC, Pettitt DJ et al. Segregation analysis of diabetic nephropathy in Pima Indians. Diabetes 2000; 49: 1049–1056.

20. Fogarty DG, Hanna LS, Wantman M et al. Segregation analysis of urinary albumin excretion in families with type 2 diabetes. Diabetes 2000; 49: 1057–1063.

21. Imperatore G, Knowler WC, Nelson RG et al. Genetics of diabetic nephropathy in the Pima Indians. Curr Diab Rep 2001; 1: 275–281.

22. Vardarli I, Baier LJ, Hanson RL et al. Gene for susceptibility to diabetic nephropathy in type 2 diabetes maps to 18q22.3–23. Kidney Int 2002; 62: 2176–2183.

23. Imperatore G, Hanson RL, Pettitt DJ et al. Sib-pair linkage analysis for susceptibility genes for microvascular complications among Pima Indians with type 2 diabetes. Pima Diabetes Genes Group. Diabetes 1998; 47: 821–830.

24. Moczulski DK, Rogus JJ, Antonellis A et al. Major susceptibility locus for nephropathy in type 1 diabetes on chromosome 3q: results of novel discordant sib-pair analysis. Diabetes 1998; 47: 1164–1169.

25. Yu H, Bowden DW, Spray BJ et al. Linkage analysis between loci in the renin-angiotensin axis and end- stage renal disease in African Americans. J Am Soc Nephrol 1996; 7: 2559–2564.

26. Lander E, Kruglyak L. Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nat Genet 1995; 11: 241–247.

27. Fogarty DG, Rich SS, Hanna L et al. Urinary albumin excretion in families with type 2 diabetes is heritable and genetically correlated to blood pressure. Kidney Int 2000; 57: 250–257.

28. Freedman BI, Beck SR, Rich SS et al. A genome–wide scan for urinary albumin excretion in hypertensive families. Hypertension 2003; 42: 291–296.

29. Ward R. Familial aggregation and genetic epidemiology of blood pressure. In: Laragh J (ed). Hypertension: Pathophysiology, Diagnosis and Management. New York: Raven Press 1990: 81–100.

30. DeWan AT, Arnett DK, Atwood LD et al. A genome scan for renal function among hypertensives: the HyperGEN study. Am J Hum Genet 2001; 68: 136–144.

31. Warram JH, Scott LJ, Hanna LS et al. Progression of microalbuminuria to proteinuria in type 1 diabetes: nonlinear relationship with hyperglycemia. Diabetes 2000; 49: 94–100.

32. Freedman BI, Bowden DW, Rich SS et al. Genetic initiation of hypertensive and diabetic nephropathy. Am J Hypertens 1998; 11: 251–257.

33. Brown DM, Provoost AP, Daly MJ et al. Renal disease susceptibility and hypertension are under independent genetic control in the fawn–hooded rat. Nat Genet 1996; 12: 44–51.

34. Freedman BI, Rich SS, Yu H et al. Linkage heterogeneity of end-stage renal disease on human chromosome 10. Kidney Int 2002; 62: 770–774.

35. Hunt SC, Hasstedt SJ, Coon H et al. Linkage of creatinine clearance to chromosome 10 in Utah pedigrees replicates a locus for end-stage renal disease in humans and renal failure in the fawnhooded rat. Kidney Int 2002; 62: 1143–1148.

36. Iyengar SK, Fox KA, Schachere M et al. Linkage analysis of candidate loci for end-stage renal disease due to diabetic nephropathy. J Am Soc Nephrol 2003; 14: S195–S201.

37. Staessen JA, Wang JG, Ginocchio G et al. The deletion/insertion polymorphism of the angiotensin converting enzyme gene and cardiovascular-renal risk. J Hypertens 1997; 15: 1579–1592.

38. Fujisawa T, Ikegami H, Kawaguchi Y et al. Meta-analysis of association of insertion/deletion polymorphism of angiotensin I-converting enzyme gene with diabetic nephropathy and retinopathy. Diabetologia 1998; 41: 47–53.

39. Kunz R, Bork JP, Fritsche L et al. Association between the angiotensin-converting enzyme-insertion/deletion polymorphism and diabetic nephropathy: amethodologic appraisal and systematic review. J Am Soc Nephrol 1998; 9: 1653–1663.

40. Hadjadj S, Fanelli A, Torremocha F et al. Prospective follow-up study of renal function in type 2 diabetes. Arch Mal Coeur Vaiss 2001; 94: 928–932.

41. Jacobsen P, Tarnow L, Carstensen B et al. Genetic variation in the Renin-Angiotensin system and progression of diabetic nephropathy. J Am Soc Nephrol 2003; 14: 2843–2850.

42. Krolewski AS, Warram JH, Valsania P et al. Evolving natural history of coronary artery disease in diabetes mellitus. Am J Med 1991; 90: 56S–61S.

43. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998; 352: 837–853.

44. Lee KE, Klein BE, Klein R. Familial aggregation of components of the multiple metabolic syndrome in the Framingham Heart and Offspring Cohorts: Genetic Analysis Workshop Problem 1. BMC Genet 2003; 4(Suppl 1): S94.

45. Narayan KM, Pettitt DJ, Hanson RL et al. Familial aggregation of medial arterial calcification in Pima Indians with and without diabetes. Diabetes Care 1996; 19: 968–971.

46. Wagenknecht LE, Bowden DW, Carr JJ et al. Familial aggregation of coronary artery calcium in families with type 2 diabetes. Diabetes 2001; 50: 861–866.

47. Lange LA, Bowden DW, Langefeld CD et al. Heritability of carotid artery intima-medial thickness in type 2 diabetes. Stroke 2002; 33: 1876–1881.

48. Cambien F, Poirier O, Lecerf L et al. Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction. Nature 1992; 359: 641–644.

49. Samani NJ, Thompson JR, O’Toole L et al. Ameta-analysis of the association of the deletion allele of the angiotensinconverting enzyme gene with myocardial infarction. Circulation 1996; 94: 708–712.

50. Agerholm-Larsen B, Nordestgaard BG, Tybjaerg-Hansen A. ACE gene polymorphism in cardiovascular disease: meta-analyses of small and large studies in whites. Arterioscler Thromb Vasc Biol 2000; 20: 484–492.

51. Keavney B, McKenzie C, Parish S et al. Large-scale test of hypothesised associations between the angiotensin-convertingenzyme insertion/deletion polymorphism and myocardial infarction in about 5 000 cases and 6 000 controls. International Studies of Infarct Survival (ISIS) Collaborators. Lancet 2000; 355: 434–442.

52. Škrha J. Diabetes mellitus – a risk factor for cardiovascular diseases. Vnitř Lék 2001; 47(5): 281–284.

53. Krušová D. Antihypertensives and their importance in the initial stages of diabetic nephropathy. Vnitř Lék 1999; 45(11): 664–669.

54. Krahulec B, Vozar J. Incidence of risk factors and vascular complications in patients with newly diagnosed type 2 diabetes mellitus. Vnitř Lék 2002; 48(11): 1031–1038.

55. Morgan CL, Currie CJ, Stott NC et al. The prevalence of multiple diabetes-related complications. Diabet Med 2000; 17: 146–151.

56. Rychlík I, Sulková S. Diabetes mellitus and chronic renal insufficiency. Vnitř Lék 2003; 49(5): 395–402.

57. Monhart V. Hypertension and chronic renal insufficiency-chronic kidney failure. Vnitř Lék 2003; 49(5): 388–394.

58. Lindner TH, Monks D, Wanner C et al. Genetic aspects of diabetic nephropathy. Kidney Int 2003; Suppl. S186–S191.

59. Krolewski AS, Ng DP, Canani LH et al. Genetics of diabetic nephropathy: how far are we from finding susceptibility genes? Adv Nephrol Necker Hosp 2001; 31: 295–315.

60. Bowden DW. Genetics of diabetes complications. Curr Diab Rep 2002; 2: 191–200.

61. Genetic determinants of diabetic nephropathy: The family investigation of nephropathy and diabetes (FIND). J Am Soc Nephrol 2003; 14: S202–S204.