Individuals With IL-12 Component Gene Variants Have Higher Risk For Type 1 Diabetes

Up to 800,000 people in the United States are estimated to have type 1 diabetes (T1D), a disease involving the destruction of the insulin-producing cells of the pancreas and influenced by complex environmental and genetic factors. Until now, only the histocompatibility genes--which influence immune response--have been implicated in T1D. Grant Morahan and colleagues (of the Walter and Eliza Hall Institute for Medical Research in Melbourne, Australia) have now found that individuals who have specific variants of the gene encoding one component of interleukin 12 (IL-12) have a higher risk of developing T1D (Nature Genetics, Vol. 27, Issue 2, 01 Feb 2001).

IL-12 is a cytokine; as such, it mediates the signals that the different cells of the immune system send to each other during response to infection. When injected in an animal model of T1D, the non-obese diabetic (NOD) mouse, IL-12 activates a specific cell type, the Th1 class of helper T lymphocytes. In an 'autoimmune' reaction, these cells orchestrate the destruction of the insulin-producing pancreatic beta-cells, which is the hallmark of type 1 diabetes. Previous searches for genes predisposing to T1D had failed to detect the contribution of IL-12. Inspired by the NOD mouse model, Grant Morahan and colleagues applied more refined statistical 'filters' and discovered the association between some variants of the gene encoding one subunit of IL-12 and T1D. They also observed that the gene variants that confer risk drive a higher rate of production of IL-12 in cultured cells--which could explain the higher risk. As Luciano Adorini (of Roche Milano Ricerche, in Milan, Italy) argues in an accompanying News & Views article, this study not only confirms the NOD mouse as a useful model; it may also lead to a better understanding of other autoimmune diseases and validate immunotherapies currently under development.

CONTACT:

Dr. Grant Morahan
The Walter & Elizabeth Hall
Institute of Medical Research
Royal Melbourne Hospital
Victoria, Australia
Telephone: +61 3 9345 2555
Fax: +61 3 9347 0852
e-mail: morahan@wehi.edu.au

Dr. Luciano Adorini
Roche Milano Ricerche
Milano, Italy
Telephone: +39 02-288-4816
Fax: +39- 02-215-3203
e-mail: luciano.adorini@roche.com

Dr. Glenys Thomson
Department of Integrative Biology
University of California
Berkeley, California
Telephone: +1 (510) 642-7025
FAX: +1 (510) 643-5144
e-mail: glenys@allele5.biol.berkeley.edu

(C) Nature Genetics press release.

Message posted by: Trevor M. D'Souza