Study of interleukin-10 promoter region polymorphisms (-1082A/G,-819T/C and-592A/C) in type 1 diabetes mellitus in Turkish population

Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by progressive destruction of islet β-cells (Atkinson and MacLaren 1994). It apparently arises from T-cell dependent destruction of β-cells in genetically susceptible individuals (Eisenbarth 2005). The cytokines secreted by CD4 T helper type 1 and 2 (Th1 and Th2) cells may play a crucial role in the pathogenesis of T1DM (Almawi et al. 1999). Cytokines can be classified into two groups: Th1 (proinflammatory) cytokines such as TNF-α and interleukin 1, and Th2 (anti-inflammatory) cytokines such as interleukin 10 and interleukin 4 (Keen 2002). Although the exact roles that Th1 and Th2 cells play in IDDM pathogenesis remain to be established, it was suggested that Th1 cytokines promote, whereas Th2 cytokines protect from the diabetes progression (Rapoport et al. 1993; Pennline et al. 1994). It is thought that the onset and progression of T1DM results from an altered balance between Th1 and Th2 cells (Almawi et al. 1999). IL-10 is a pleiotropic Th2 cytokine that is usually considered to have a role in the downregulation of cell mediated and cytotoxic inflammatory responses, thus being a potent anti-inflammatory mediator. It has been suggested that Th2 induced component of anti-β cell immunity is mediated principally by IL-10 (Lee et al. 1994, 1996; Pakala et al. 1997). Approximately 75% of the variation in IL-10 production appears to be genetically determined (Westendorp et al. 1997). The gene encoding IL-10 has been mapped to chromosome 1q. Several polymorphic sites within the promoter region have been described, including two microsatellite polymorphisms and three biallelic polymorphisms at