Plasma protein N-glycan signatures of type 2 diabetes
Plasma protein N-glycan signatures of type 2 diabetes
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DOI：
10.1016/j.bbagen.2018.08.005
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发表时间：
2018-12-01
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：
Dotz, Viktoria;Lemmers, Roosmarijn F. H.;van Hoek, Mandy
背景资料：关于2型糖尿病中的酶促N-糖基化知之甚少，这是一种常见的蛋白质翻译后修饰，影响其功能并整合遗传和环境影响。我们试图深入了解N-糖基化，发现尚未探索的病理生理机制在2型diabetes.Methods：使用高通量MALDI-TOF质谱法，我们测量了N-聚糖的DiaGene病例对照研究（1583例和728对照）的血浆样本。相关性用逻辑回归进行研究，并校正年龄、性别、体重指数、高密度脂蛋白胆固醇、非高密度脂蛋白胆固醇和吸烟。研究结果在232例病例和108名对照的巢式重复队列中重复。结果：18个糖基化特征与2型糖尿病显著相关。糖尿病患者双触角聚糖的岩藻糖基化和二分性降低（比值比（OR）分别为0.81，p = 1.26 E-03和OR = 0.87，p = 2.84 E-02），而总唾液酸化，特别是α 2，6-连接唾液酸化增加（OR = 1.38，p = 9.92E-07和OR = 1.40，p = 5.48E-07）。三触角聚糖的α 2，3-连接唾液酸化降低（OR = 0.60，p = 6.38E-11）。结论：虽然一些糖基化变化反映了炎症，如α 2，6-连接唾液酸化增加，但我们发现2型糖尿病患者α 2，3-连接唾液酸化降低与急性和慢性炎症的报道相矛盾。因此，它可能有以前未报道的免疫学影响2型diabetes.General意义：这项研究提供了新的见解N-糖基化模式在2型糖尿病，这可以燃料的因果机制和后果的研究，这种复杂的疾病。
Background: Little is known about enzymatic N-glycosylation in type 2 diabetes, a common posttranslational modification of proteins influencing their function and integrating genetic and environmental influences. We sought to gain insights into N-glycosylation to uncover yet unexplored pathophysiological mechanisms in type 2 diabetes.Methods: Using a high-throughput MALDI-TOF mass spectrometry method, we measured N-glycans in plasma samples of the DiaGene case-control study (1583 cases and 728 controls). Associations were investigated with logistic regression and adjusted for age, sex, body mass index, high-density lipoprotein-cholesterol, non-high density lipoprotein-cholesterol, and smoking. Findings were replicated in a nested replication cohort of 232 cases and 108 controls.Results: Eighteen glycosylation features were significantly associated with type 2 diabetes. Fucosylation and bisection of diantennary glycans were decreased in diabetes (odds ratio (OR) = 0.81, p = 1.26E-03, and OR = 0.87, p = 2.84E-02, respectively), whereas total and, specifically, alpha2,6-linked sialylation were increased (OR = 1.38, p = 9.92E-07, and OR = 1.40, p = 5.48E-07). Alpha2,3-linked sialylation of triantennary glycans was decreased (OR = 0.60, p = 6.38E-11).Conclusions: While some glycosylation changes were reflective of inflammation, such as increased alpha2,6-linked sialylation, our finding of decreased alpha2,3-linked sialylation in type 2 diabetes patients is contradictory to reports on acute and chronic inflammation. Thus, it might have previously unreported immunological implications in type 2 diabetes.General significance: This study provides new insights into N-glycosylation patterns in type 2 diabetes, which can fuel studies on causal mechanisms and consequences of this complex disease.