IgG glycan patterns are associated with type 2 diabetes in independent European populations
IgG glycan patterns are associated with type 2 diabetes in independent European populations
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DOI：
10.1016/j.bbagen.2017.06.020
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发表时间：
2017-09-01
影响因子：
3
通讯作者：
van Hoek, Mandy
中科院分区：
文献类型：
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作者：
Lemmers, Roosmarijn F. H.;Vilaj, Marija;van Hoek, Mandy
背景：2型糖尿病是遗传和后天因素相互作用的结果。蛋白质上的聚糖反映了遗传、代谢和环境因素。然而，IgG聚糖与2型糖尿病的关联尚未被描述。我们比较了2型糖尿病患者与健康人的IgG N-聚糖模式。方法：在DiaGene研究中，一项基于人群的病例对照研究，分析了（1886例和854例对照）58种IgG聚糖特征。在基于人群的CROATIA-Korcula-CROATIA-Vis-ORCADES研究（162例病例和3162例对照）中重复了这些发现，并进行了荟萃分析。ROC曲线的AUC计算使用10倍交叉验证的临床特征，IgG聚糖和他们的combination.Results：广泛的临床协变量校正后，5 IgG聚糖和13个衍生性状显着相关的荟萃分析（Bonferroni校正后）2型糖尿病。将IgG聚糖添加至年龄和性别，AUC从0.542增加至0.734。将它们添加到广泛模型中并没有显著改善AUC。单独IgG聚糖的AUC为0.729。结论：一些IgG聚糖和特征与2型糖尿病密切相关，反映了促炎和生物老化状态。IgG聚糖显示AUC的改善有限。然而，IgG聚糖单独显示出良好的预测，表明它们可以捕获组合协变量的信息。这些发现可能有助于深入了解2型糖尿病的病理生理学。
Background: Type 2 diabetes results from interplay between genetic and acquired factors. Glycans on proteins reflect genetic, metabolic and environmental factors. However, associations of IgG glycans with type 2 diabetes have not been described. We compared IgG N-glycan patterns in type 2 diabetes with healthy subjects.Methods: In the DiaGene study, a population-based case-control study, (1886 cases and 854 controls) 58 IgG glycan traits were analyzed. Findings were replicated in the population-based CROATIA-Korcula-CROATIA-Vis-ORCADES studies (162 cases and 3162 controls), and meta-analyzed. AUCs of ROC-curves were calculated using 10-fold cross-validation for clinical characteristics, IgG glycans and their combination.Results: After correction for extensive clinical covariates, 5 IgG glycans and 13 derived traits significantly associated with type 2 diabetes in meta-analysis (after Bonferroni correction). Adding IgG glycans to age and sex increased the AUC from 0.542 to 0.734. Adding them to the extensive model did not substantially improve the AUC. The AUC for IgG glycans alone was 0.729.Conclusions: Several IgG glycans and traits firmly associate with type 2 diabetes, reflecting a pro-inflammatory and biologically-aged state. IgG glycans showed limited improvement of AUCs. However, IgG glycans showed good prediction alone, indicating they may capture information of combined covariates. The associations found may yield insights in type 2 diabetes pathophysiology.