Moosavi Mandana, Séguin Jade, Polychronakos Constantin
Department of Endocrinology, University of British Columbia, Vancouver, Canada.
Department of Pediatrics, McGill University, Montreal, Canada.
Pediatr Diabetes. 2017 Sep;18(6):459-462. doi: 10.1111/pedi.12421. Epub 2016 Aug 9.
To analyze the correlation between duration and depth of honeymoon phase in patients with type 1 diabetes (T1DM) and autoimmunity risk loci.
From a database of 567 individuals with clinical data, we selected 210 patients for whom we had dense genotyping results of single-nucleotide polymorphisms (SNPs) from our previous genome-wide association studies (GWAS) or targeted genotyping data. Using PLINK software, we analyzed the association between time spent in honeymoon phase as our quantitative trait, and 24 known autoimmunity predisposing SNPs.
We found one allele on chromosome 5, rs4613763 mapping to a Prostaglandin Receptor EP4 (PTGER4) to reach statistical significance (P = .0067), in determining a larger proportion of T1DM patients with a detectable honeymoon phase. This polymorphism determines risk for inflammatory bowel disease (IBD) but not T1DM.
By showing the role of PTGER4 in autoimmune diseases and its effect on inflammatory responses via its interaction with NF-kB, we hypothesize that PTGER4 modulates honeymoon phase in patients with T1DM without influencing the risk of developing T1DM. We hypothesize that this quantitative trait locus promotes inflammatory suppression of beta cells without directly promoting beta-cell destruction. Understanding SNPs that effect function can provide insight in to pathogenesis of T1DM and the mechanism of the honeymoon phase. Because this is a hypothesis-generating study, it needs to be replicated in an additional larger cohort.
分析1型糖尿病（T1DM）患者蜜月期的持续时间和深度与自身免疫风险位点之间的相关性。
从一个包含567例个体临床数据的数据库中，我们选择了210例患者，这些患者拥有我们之前全基因组关联研究（GWAS）的单核苷酸多态性（SNP）密集基因分型结果或靶向基因分型数据。使用PLINK软件，我们分析了作为定量性状的蜜月期时长与24个已知的自身免疫易感SNP之间的关联。
我们发现5号染色体上的一个等位基因rs4613763，其映射到前列腺素受体EP4（PTGER4），在确定更大比例的有可检测蜜月期的T1DM患者中达到统计学显著性（P = 0.0067）。这种多态性决定炎症性肠病（IBD）的风险，但不决定T1DM的风险。
通过显示PTGER4在自身免疫性疾病中的作用及其通过与NF-κB相互作用对炎症反应的影响，我们假设PTGER4调节T1DM患者的蜜月期，而不影响患T1DM的风险。我们假设这个数量性状位点促进β细胞的炎症抑制，而不直接促进β细胞破坏。了解影响功能的SNP可以深入了解T1DM的发病机制和蜜月期的机制。由于这是一项产生假设的研究，需要在另外一个更大的队列中进行重复验证。
