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• W1999424780 abstract "Melanoma differentiation-associated 5 (MDA5), a product of the IFIH1 gene, is responsible for sensing double-stranded viral double-stranded RNA (RNA). In this study, we showed a significant association of two rare IFIH1 variants, rs35744605 (E627X) and rs35667974 (I923V), with decreased risk of type 1 diabetes (T1D) in a Russian population (for the allele X627, odds ratio [OR] = 0.39, 95% confidence interval [95% CI] = 0.22-0.69, p = 0.0015; for the allele V923, OR = 0.45, 95% CI, 0.30-0.66, p = 5.4 × 10(-5)). We detected a 3.5-fold greater frequency of enteroviral RNA in T1D subjects compared with controls (p <1.0 × 10(-8)), and 2.1-fold more frequent presence of viral RNA in T1D patients with a recent-onset diabetes (duration ≤1 year) compared with those with a longer disease (p <1.0 × 10(-8)). The carriage of the predisposing IFIH1 EI/EI haplogenotype was significantly associated with a 1.5- to 1.7-fold increase in the poly(I:C)-stimulated secretion of IFN-β in PMBCs compared with the other IFIH1 variants. The upregulated MDA5-dependent production of inflammatory cytokines could enhance the autoimmune destruction of β-cells mediated by self-reactive T-cells." @default.
• W1999424780 created "2016-06-24" @default.
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• W1999424780 date "2010-11-01" @default.
• W1999424780 modified "2023-10-16" @default.
• W1999424780 title "Loss-of-function mutations E6 27X and I923V of IFIH1 are associated with lower poly(I:C)–induced interferon-β production in peripheral blood mononuclear cells of type 1 diabetes patients" @default.
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• W1999424780 doi "https://doi.org/10.1016/j.humimm.2010.08.005" @default.
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