Possible genetic reasons for late complications in diabetes mellitus [Mogliche genetische ursachen fur spatkomplicationen des diabetes mellitus]

被引:0
作者
Klemm T. [1 ]
Paschke R. [1 ]
机构
[1] Med. Klin. Poliklin. III der Univ., D-04103 Leipzig
关键词
Angiopathy; Diabetes mellitus; Genetic variation; Genetics; Nephropathy; Neuropathy; Retinopathy;
D O I
10.1007/BF03044978
中图分类号
学科分类号
摘要
Background: Hyperglycemia occurs in every patient with diabetes mellitus. It is the most important factor in the development of diabetic complications. However, the onset, intensity and the progression of complications show large interindividual variations. Manifestation in families and the lack of complications in some diabetics with poor metabolic control indicate a genetic predisposition to develop diabetic complications like nephropathy, neuropathy and angiopathy. Nephropathy: Diabetic nephropathy occurs only in 25 to 40% of the diabetic patients. Therefore a genetic risk factor for this complication is very likely. Various variations in genes like ACE-gene and angiotensinogen-gene have been described, which could be associated with the developement of diabetic nephropathy. Neuropathy: Peripheral diabetic neuropathy occurs in up to 66% of all diabetics. Therefore and because of the possible pathological mechanisms genetic risk factors like variations in the Na/K-ATPase-gene and in the aldose reductase-gene are discussed. Retinopathy. An association between diabetic retinopathy and polymorphisms in the ACE-gene and the aldose reductase-gene seems very unlikely, because up to 75% of the diabetic patients suffer from retinopathy after 15 years of diabetes. Macroangiopathy: A large number of studies show an association between diabetic macroangiopathy and genetic variations in the ACE-gene (I/D-variant) and the paraoxonase-gene (2 isoforms). Conclusion: Based on the current evidence for associations of genetic markers with diabetic complications, the generation of an individual risk profile based on genetic markers seems to be possible. In addition to near euglycemia genetic markers could direct therapeutic strategies and lead to new therapeutic approaches.
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页码:31 / 39
页数:8
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  • [1] Adkins S., Gan K.N., Mody M., Et al., Molecular basis for the polymorphic forms of human serum paraoxonase/arylesterase: Glutamine or arginine at position 191, for a respective A or B allozymes, Am J Hum Genet, 52, pp. 598-608, (1993)
  • [2] Antikainen M., Murtomaki S., Syvanne M., Et al., The Gln-Arg 191 polymorphism of the human paraoxonase gene (HUMPONA) is not associated with the risk of coronary artery disease in Finns, J Clin Invest, 98, pp. 883-885, (1996)
  • [3] Arruda V.R., Von Zuben P.M., Chiaparini L.C., The mutation Ala677Val in the methylenetetrahydrofolat reductase gene: A risk factor for arterial disease and venous thrombosis, Thromb Haemost, 77, pp. 818-821, (1997)
  • [4] Ballard D.J., Humphrey L.L., Melton L.J. III, Et al., Epidemiology of persistent proteinuria in type II diabetes mellitus. Population-based study in Rochester, Minnesota, Diabetes, 37, pp. 405-412, (1998)
  • [5] Barnas U., Schmidt A., Illievich A., Et al., Evaluation of risk factors for the development of nephropathy in patients with IDDM: Insertion/deletion angiotensin converting enzyme gene polymorphism, hypertension and metabolic control, Diabetologia, 40, pp. 327-331, (1997)
  • [6] Blatter-Garin M.-C., James R.W., Dussoix P., Et al., Paraoxonase polymorphism Met-Leu 34 is associated with modified serum concentrations of the enzyme, J Clin Invest, 99, pp. 62-66, (1997)
  • [7] Boize R., Benhamon P.-Y., Corticelli P., Et al., Apo E polymorphism and albuminuria in diabetes mellitus: A role dor LDL in the development of nephropathy in NIDDM?, Nephrol Dial Transplant, 13, pp. 72-75, (1998)
  • [8] 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, 359, pp. 641-644, (1992)
  • [9] Cameron N.E., Cotter M.A., Dines K.C., Et al., Aldose reductase inhibition, nerve perfusion, oxygenation and function in streptozotocin-diabetic rats: Dose-response considerations and independence from a myo-inositol mechanism, Diabetologia, 37, pp. 651-663, (1997)
  • [10] Caprio S., Wong S., Alberti K.G.M.M., Cardiovascular complications of diabetes, Diabetologia, 40, (1997)