2021  1,540
2020  1,374
2019  1,023
2018  0,932
2017  0,977
2016  0,799
2015  0,662
2014  0,740
2013  0,739
2012  0,637
2011  0,658
2010  0,654
2009  0,570
2008  0,849
2007  0,805
2006  0,330
2005  0,435
2004  0,623
2003  0,567
2002  0,641
2001  0,490
2000  0,477
1999  0,762
1998  0,785
1997  0,507
1996  0,518
1995  0,502
Vol 42(2008) N 5 p. 773-783;
V.V. Nosikov, Yu.A. Seregin

Molecular genetics of type 1 diabetes mellitus: Achievements and future trends

State Research Center GosNIIgenetika, Moscow, 117545, Russia
Received - 2008-04-01; Accepted - 2008-04-01

Type 1 diabetes mellitus (T1DM) is a widespread severe disease that results from autoimmune destruction of β cells in Langerhans islets of the pancreas. To date, several loci involved in T1DM have been reliably identified using various approaches: the MHC locus, VNTR within the 5'-nontranscibed region of the insulin gene (INS), CTLA4 (T-cell surface receptor), PTPN22, PTPN2 (T-cell tyrosine phosphatases), IL2 (interleukin 2, IL-2), IL2RA (IL-2 receptor α chain), KIAA0350 (unknown function), and IFIH1 (receptor for double-stranded DNA generated in virus infections). Functional analysis of their protein products confirmed the hypothesis that T1DM is underlain by deregulation of the mechanisms of immune tolerance and, on the other hand, a destructive immune response against the body's own proteins after virus infection or some other immune stress. Thus the protein products of MHC, INS, PTPN22, and PTPN2 are involved in the intrathymic formation of the T-cell repertoire, responsible for immune defense of the body. On the other hand, nonspecific activation of T cells, which starts autoimmune destruction of pancreatic β cells, is most likely associated with the protein products of CTLA4, IL2, IL2RA, and, possibly, PTPN22 and PTPN2. Apart from the genes with unknown functions, the only exception is IFIH1, but its association with T1DM confirms that certain virus infections can activate autoreactive T cells and lead to T1DM.

type 1 diabetes mellitus, candidate genes, genome searches, MHC locus, insulin gene (INS), CTLA4, PTPN22, PTPN2, IL2, IL2RA, KIAA0350, IFIH1