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Mueller, Guenter (2010): Personalized Prognosis and Diagnosis of Type 2 Diabetes - Vision or Fiction? In: Pharmacology, No. 3: pp. 168-187 [PDF, 1MB]

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Typical civilization diseases, such as type 2 diabetes, share several features: their worldwide frequency, the complexity of the underlying pathogenic mechanisms, heterogeneity in the phenotypes and their multifactorial nature due to a wide variety of possible combinations of disease susceptibility or protective genes in different tissues and negative or positive environmental factors. This is in sharp contrast to classical inherited diseases, such as Huntington's chorea, which are often caused by complete loss- or gain-of-function mutations in a single gene. The causative polymorphisms of susceptibility genes, however, are characterized by relatively subtle alterations in the function of the corresponding gene products, i.e. low penetrance and effect size, which do not support the pathogenesis per se, and by their high frequency; these two characteristics result in high expenditures for their identification and a rather low predictive value. In the future, the reliable and early diagnosis of common diseases will thus depend on the determination of all (or as many as possible) polymorphisms of each susceptibility gene together with the corresponding gene products and the metabolites emerging thereof for each individual. Great hopes are currently associated with systems biology to cover these demands in time (i.e. along the pathogenesis) and space (i.e. in all relevant tissues). Copyright (C) 2010 S. Karger AG, Basel

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