Abstract
BackgroundThe genetic basis of the autoimmune disease type 1 diabetes (T1D) has now been largely determined, so now we can compare these findings with emerging genetic knowledge of disorders and phenotypes that have been negatively or positively associated with T1D historically. Here, we assessed the role in T1D of variants previously reported to be associated with atopic diseases and epithelial barrier function, profilaggrin (), and those that affect the expression levels of the proinflammatory cytokines tumour necrosis factor (TNF)-α, interleukin (IL)-1β, interferon (IFN)γ and IL-18.MethodsWe genotyped single nucleotide polymorphisms (SNPs): − 105/rs28665122 in SELS or SEPS1 (selenoprotein), three single nucleotide polymorphisms in IL18 (−105/rs360717, + 183/rs5744292 and + 1467/rs574456) and R501X/rs61816761 in FLG, the major locus associated with atopic dermatitis and predisposing to asthma, in a minimum of 6743 T1D cases and 7864 controls.ResultsNo evidence of T1D association was found for any of the SNPs we genotyped at FLG, SELS or IL18 (p ≥ 0.03), nor with haplotypes of IL18 (p = 0.82). Review of previous T1D genome-wide association results revealed that four (human leucocyte antigen (HLA), gasdermin B/ORM1 (Saccharomyces cerevisiae)-like/gasdermin B/, GSDMB/ORMDL3/GSDMA and IL2RB) of ten loci recently reported to be associated with asthma were associated with T1D (p≤0.005).ConclusionsThese results show that there are shared genetic associations for atopy-related traits and T1D, and this might help in the future to understand the mechanisms, pathways and environmental factors that underpin the rapid rise in incidence of both disorders in children. Copyright © 2011 John Wiley & Sons, Ltd.
Highlights
Type 1 diabetes (T1D) is a multifactorial autoimmune disease which results from cell-mediated immune destruction of pancreatic β cells, a complex process controlled by many genes, in particular, the human leucocyte antigen (HLA) class II and class I genes [1]
We investigated whether single nucleotide polymorphism (SNP) in Selenoprotein S (SELS), IL18 and FLG were associated with type 1 diabetes (T1D)
The three SNPs associated with IL18 levels, −105/rs5744292, +1467/rs5744256 and +183/rs360717, were not associated with T1D (p ≥ 0.03; Table 3), nor were the IL18 haplotypes defined by the two SNPs −105/rs5744292 and +183/rs360717 (p = 0.82; Table 4), which have been shown to be associated with decreased IL-18 levels [16,25]
Summary
Type 1 diabetes (T1D) is a multifactorial autoimmune disease which results from cell-mediated immune destruction of pancreatic β cells, a complex process controlled by many genes, in particular, the human leucocyte antigen (HLA) class II and class I genes [1]. T1D shares this childhood pandemic with asthma, allergy and atopic illnesses, suggesting perhaps common environmental factors and susceptibility alleles [1,3,4]. Stene and Joner found an inverse association between atopic dermatitis and T1D [6], supporting the EURODIAB substudy which found a reduced risk of T1D in children exhibiting atopic eczema [7]. Another group found that asthma was more common in children with T1D than those without in a Finnish birth register study, suggesting that Th1 and Th2 immune-mediated disorders can coexist [8]. We assessed the role in T1D of variants previously reported to be associated with atopic diseases and epithelial barrier function, profilaggrin (FLG), and those that affect the expression levels of the proinflammatory cytokines tumour necrosis factor (TNF)-α, interleukin (IL)-1β, interferon (IFN)γ and IL-18
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