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Wiener Medizinische Wochenschrift

, Volume 158, Issue 1–2, pp 2–12 | Cite as

Genetics of autoimmune diabetes mellitus

  • Marie ČernáEmail author
Themenschwerpunkt

Summary

Autoimmune diabetes mellitus, called type 1 diabetes mellitus (T1DM), is caused by autoimmune destruction of islet beta cells in the pancreas. T1DM susceptibility loci mapped by different genome screening are IDDM1-IDDM18. It has been estimated that HLA (IDDM1) provides up to 40–50 % of the familial clustering of T1DM (LOD score of 65.8). Many studies have verified that DQB1*0302 is a strong susceptibility gene and that the heterozygous combination of DQA1*0301-DQB1*0302 on the HLA-DR4 haplotype and DQA1*0501-DQB1*0201 on the HLA-DR3 haplotype results in a synergistically increased risk of T1DM. The presence of predisposing genes in autoimmune diabetes decreases with age, probably due to increasing influence of environmental factors. Autoimmune diabetes with manifestation in adults may have partly different immunogenetic etiopathogenesis than autoimmune diabetes with manifestation in childhood. Compared to fast progressing adult-onset T1DM, slowly progressing adult-onset type 1 diabetes (LADA) might involve genes leading to a slow progressive β-cells destruction.

Keywords

Type 1 diabetes mellitus LADA IDDM HLA Autoantibodies 

Genetik des autoimmunen Diabetes mellitus

Zusammenfassung

Der autoimmune Diabetes mellitus, auch Typ 1 Diabetes mellitus (T1DM) genannt, wird durch die autoimmune Zerstörung der Beta-Zellen in den Langerhanschen Inseln des Pankreas hervorgerufen. Mittels verschiedener genomischer Screenings wurden IDDM1-IDDM18 als T1DM-Suszeptibilitäts-Loci identifiziert. Es wurde geschätzt, dass HLA (IDDM1) für bis zu 40–50 % der familiären Häufung verantwortlich ist. In einer Vielzahl von Studien konnte bestätigt werden, dass DQB1*0302 ein starkes Suszeptibilitäts-Gen ist, und dass die heterozygote Kombination von DQA1*0301-DQB1*0302 beim HLA-DR4 Haplotypus und DQA1*5001-DQB1*0201 beim HLA-DR3 Haplotyp in einem synergistisch erhöhten Risiko für den T1DM resultiert. Der Einfluss von prädisponierenden Genen beim autoimmunen Diabetes mellitus nimmt mit dem Alter ab, wahrscheinlich aufgrund der steigenden Bedeutung von Umweltfaktoren. Der autoimmune Diabetes, der sich im Erwachsenenalter manifestiert, hat gegenüber dem autoimmunen Diabetes des Kindesalters eine teilweise unterschiedliche immunogenetische Ätiophatogenese. Neben dem rasch fortschreitenden T1DM mit Manifestation im Erwachsenenalter wird auch ein sich langsam entwickelnde Typ 1 Diabetes (LADA) unterschieden. Bei dieser Form dürften die beteiligten Gene zu einer nur langsam progressiven Beta-Zell-Destruktion führen.

Schlüsselwörter

Typ1 Diabetes mellitus LADA Insulin- abhängiger Diabetes mellitus HLA- System Autoantikörper 

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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  1. 1.Department of Cellular and Molecular Biology, Third Faculty of MedicineCharles UniversityPrahaCzech Republic

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