Genetic determinants of diabetes are similarly associated with other immune-mediated diseases.
OBJECTIVE
I discuss the increasing number of genes discovered to exert pleiotropic action on susceptibility to diabetes and simultaneously to other immune-mediated diseases. While a genetic correlation between type 1 diabetes and autoimmunity is not surprising, the mechanism of a relationship to other conditions such as atopy is less obvious. The recent wave of genome-wide association studies offers confirmation of previously recognized risk loci, but also novel loci that also are likely to act via multiple pathogenetic pathways. I will review this material more in a genetical than an immunological way.


RESULTS
Identification of IFIH1, an RNA helicase involved in the innate immune response to viral infection as a risk factor for type 1 diabetes and rheumatoid arthritis. Confirmation of the roles of CTLA4 and PTPN22 as general immune function modulators with a nonlinear dose-response effect on autoimmunity, and confirmation of the role of IL2RA, which may act via a regulatory T cell subset on immune disease risk. Expansion of the role of PPARG in immunity.


CONCLUSIONS
The wave of genome-wide association studies already experienced in the last 2 years has solidified what we thought we knew and added a list of genes in new pathways. The association of IFIH1 with type 1 diabetes may offer a real window into early events in the development of that disease.
Duffy
David L
DL
Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Herston, Queensland, Australia. David.Duffy@qimr.edu.au
D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D000943:Antigens, Differentiation / Q000235:genetics / Q000276:immunology; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology; D060908:CTLA-4 Antigen; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D020022:Genetic Predisposition to Disease; D006801:Humans; D007154:Immune System Diseases / Q000235:genetics* / Q000276:immunology; D000072640:Interferon-Induced Helicase, IFIH1; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics / Q000276:immunology; D047495:PPAR gamma / Q000235:genetics / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics / Q000276:immunology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D047495:PPAR gamma; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; C452815:IFIH1 protein, human; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1