Immunoglobulin G N-Glycosylation Signatures in Incident Type 2 Diabetes and Cardiovascular Disease.
Immunoglobulin G N-Glycosylation Signatures in Incident Type 2 Diabetes and Cardiovascular Disease.
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N-糖基化是免疫球蛋白（Ig）的功能性翻译后修饰。我们假设特异性IgG N-聚糖与2型糖尿病和心血管疾病（CVD）相关。我们在基于人群的欧洲癌症与营养前瞻性研究（EPIC）-波茨坦队列（2型糖尿病子队列2,127例[741例发病病例]; CVD子队列2,175例[417例心肌梗死和卒中病例]）中进行了病例队列研究。超高效液相色谱法测定24个IgG N-聚糖峰（IgG-GPs）的相对丰度，并根据结构相似性推导出8个糖基化性状。用分数多项式预选终点相关IgG-GP，用混杂因素校正的考克斯模型估计前瞻性相关性。糖尿病风险相关性在三项独立研究中得到验证。校正混杂因素和多重检验校正后，IgG-GP 7、IgG-GP 8、IgG-GP 9、IgG-GP 11和IgG-GP 19与2型糖尿病风险相关。在EPIC-Potsdam和独立验证研究中，基于这些IgG-GP的评分与较高的糖尿病风险相关（总计843例病例，总计3，149例非病例，合并估计值每SD增加1.50 [95% CI 1.37-1.64]）。IgG-GPs与CVD风险的关联在男性和女性之间存在差异。在女性中，IgG-GP 9与CVD风险呈负相关（风险比[HR]/SD 0.80 [95% CI 0.65-0.98]）。在男性中，基于IgG-GP 19和IgG-GP 23的加权评分与较高的CVD风险相关（HR/SD 1.47 [95% CI 1.20-1.80]）。此外，几个衍生性状与心脏代谢疾病的发病率相关。选定的IgG N-聚糖与经典风险因素（包括临床生物标志物）以外的心脏代谢风险相关。
N-glycosylation is a functional posttranslational modification of immunoglobulins (Igs). We hypothesized that specific IgG N-glycans are associated with incident type 2 diabetes and cardiovascular disease (CVD). We performed case-cohort studies within the population-based European Prospective Investigation into Cancer and Nutrition (EPIC)–Potsdam cohort (2,127 in the type 2 diabetes subcohort [741 incident cases]; 2,175 in the CVD subcohort [417 myocardial infarction and stroke cases]). Relative abundances of 24 IgG N-glycan peaks (IgG-GPs) were measured by ultraperformance liquid chromatography, and eight glycosylation traits were derived based on structural similarity. End point–associated IgG-GPs were preselected with fractional polynomials, and prospective associations were estimated in confounder-adjusted Cox models. Diabetes risk associations were validated in three independent studies. After adjustment for confounders and multiple testing correction, IgG-GP7, IgG-GP8, IgG-GP9, IgG-GP11, and IgG-GP19 were associated with type 2 diabetes risk. A score based on these IgG-GPs was associated with a higher diabetes risk in EPIC-Potsdam and independent validation studies (843 total cases, 3,149 total non-cases, pooled estimate per SD increase 1.50 [95% CI 1.37–1.64]). Associations of IgG-GPs with CVD risk differed between men and women. In women, IgG-GP9 was inversely associated with CVD risk (hazard ratio [HR] per SD 0.80 [95% CI 0.65–0.98]). In men, a weighted score based on IgG-GP19 and IgG-GP23 was associated with higher CVD risk (HR per SD 1.47 [95% CI 1.20–1.80]). In addition, several derived traits were associated with cardiometabolic disease incidence. Selected IgG N-glycans are associated with cardiometabolic risk beyond classic risk factors, including clinical biomarkers.
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影响因子：
82.9
作者：
通讯作者：
--
DOI：
10.1074/mcp.m111.010090
发表时间：
2011-10
期刊：
Molecular & cellular proteomics : MCP
影响因子：
--
作者：
Pucić M;Knezević A;Vidic J;Adamczyk B;Novokmet M;Polasek O;Gornik O;Supraha-Goreta S;Wormald MR;Redzić I;Campbell H;Wright A;Hastie ND;Wilson JF;Rudan I;Wuhrer M;Rudd PM;Josić D;Lauc G
通讯作者：
Lauc G
DOI：
10.1016/j.bbagen.2017.06.020
发表时间：
2017-09-01
影响因子：
3
作者：
Lemmers, Roosmarijn F. H.;Vilaj, Marija;van Hoek, Mandy
通讯作者：
van Hoek, Mandy
影响因子：
5.4
作者：
Akinkuolie, Akintunde O.;Buring, Julie E.;Mora, Samia
通讯作者：
Mora, Samia
DOI：
10.1016/j.bbagen.2018.08.005
发表时间：
2018-12-01
影响因子：
3
作者：
Dotz, Viktoria;Lemmers, Roosmarijn F. H.;van Hoek, Mandy
通讯作者：
van Hoek, Mandy