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Joslin researchers increase understanding of genetic risk factor for type 1 diabetes
Date:11/28/2012

BOSTON November 28, 2012 As part of their ongoing research on the role of genes in the development of type 1 diabetes, Joslin Diabetes Center scientists, in collaboration with scientists at the University of Wrzburg, have demonstrated how a genetic variant associated with type 1 diabetes and other autoimmune diseases influences susceptibility to autoimmunity. The findings appear in the upcoming issue of Diabetes.

Recent studies of the human genome have identified genetic regions associated with autoimmune diseases such as type 1 diabetes. Joslin scientists in the Section of Immunobiology seek to understand how genes that are most widely associated with various autoimmune diseases contribute to disease risk.

One of these genes is PTPN22, which plays a role in lymphocyte (immune cell) function. A PTPN22 variant (or mutation) has been implicated as a risk factor for type 1 diabetes and several other autoimmune disorders. PTPN22 is involved in the formation of a key protein known as lymphoid tyrosine phosphatase (LYP), which helps control the activity of T and B cells in the immune system. The PTPN22 mutation generates a variation of LYP with a different molecular structure.

Most studies of the PTPN22 disease variant have suggested that this variant is a gain-of-function genetic mutation that enhances LYP activity and lessens the activity of T and B cells, which increases susceptibility to autoimmunity. "When immune cells are less reactive during the maturation phase of their development, the cells can evade mechanisms that help protect against autoimmunity," says study lead author Stephan Kissler, PhD, of the Section of Immunobiology. However, one study which analyzed data from humans and genetically modified mice suggested that the LYP variant associated with type 1 diabetes is a loss-of-function mutation that reduces LYP activity.

To help resolve the conflicting data, Joslin scientists conducted studies with a unique
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Contact: Jeffrey Bright
jeffrey.bright@joslin.harvard.edu
617-309-1957
Joslin Diabetes Center
Source:Eurekalert  

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