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Association of TNF-α and PTPN22 SNPs with the risk and clinical outcome of type 1 diabetes


Type 1 Diabetes mellitus (T1DM) begins with aberrant inflammatory process followed by auto-destruction in genetically susceptible individuals. Therefore, we hypothesized that gain-of-function allelic variants TNF-α-238A, -308A and PTPN22 1858T could be associated not only with T1DM development but also with the clinical outcome in patients of Bosnia and Herzegovina. A total of 402 subjects were enrolled in the association study. SNPs were determined by PCR-RFLP. Data was analyzed by GraphPad Prism and Sigma Stat 3.5 software. Genotypes frequencies at TNF-α-238 and -308 loci were not statistically different between patients and controls. In contrast, distribution of genotypes at the 1858 position of PTPN22 was significantly different, due to higher frequency of gain-of-function gene variants in patients than controls. Moreover, long term glucose regulation (based on HbA1c level) was significantly worse in patients with the risk TNF-α-308A allele than in patients with non-risk (G) allele. However, patients with the risk allele of both genes (TNF-α-308A and PTPN22 1858T) had the worst glycemic control, suggesting that those two work synergistically. In conclusion, in a cohort from Bosnia and Herzegovina TNF-α-308A allele is significantly associated with the worse long-term glucose control, but PTPN22 1858T allele is significantly associated with diabetes development.

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Correspondence to Marijana Popović Hadžija.

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Hadžija, M.P., Korolija, M., Vukadinović, G. et al. Association of TNF-α and PTPN22 SNPs with the risk and clinical outcome of type 1 diabetes. cent.eur.j.biol. 8, 513–519 (2013).

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  • Polymorphism
  • Autoimmunity
  • Cytokine