N-glycosylation of immunoglobulin G predicts incident hypertension.
N-glycosylation of immunoglobulin G predicts incident hypertension.
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DOI：
10.1097/hjh.0000000000002963
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发表时间：
2021-12-01
影响因子：
4.9
通讯作者：
Menni C
中科院分区：
文献类型：
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作者：
Kifer D;Louca P;Cvetko A;Deriš H;Cindrić A;Grallert H;Peters A;Polašek O;Gornik O;Mangino M;Spector TD;Valdes AM;Padmanabhan S;Gieger C;Lauc G;Menni C
免疫球蛋白 G (IgG) 的糖基化是免疫系统的重要调节剂，与流行的高血压有关。本研究的目的是通过分析具有 2 个独立复制样本的大型女性队列中的 IgG 糖组组成，探讨 IgG 糖组在高血压诊断之前是否开始发生变化。我们纳入了来自 TwinsUK 队列的 989 名不相关的高血压病例和 1628 名对照者（平均随访时间为 6.3 年），通过超高效液相色谱和纵向血压测量在基线时测量 IgG。我们在 10001 只斑点狗中的 106 只个体和 KORA S4 中的 729 只个体中重复了我们的研究结果。在调整年龄、平均动脉压、体重指数、家庭相关性和多重测试（FDR < 0.1）后，应用 Cox 回归混合模型来识别高血压发病前聚糖特征的变化。通过利用 10001 只斑点狗中的 Cox 回归混合模型和 KORA 队列中的逻辑回归模型，在两个独立队列中复制了显着的 IgG 发病高血压关联。我们鉴定并复制了 4 个聚糖特征，即平分 GlcNAc、GP4、GP9 和 GP21 的发生率，在调整混杂因素和多重测试后，这些特征可预测高血压的发生率（HR[95%CI]范围从 GP21 的 0.45[0.24;0.84] 到 GP4 的 2.9[1.5;5.68]）。然后，我们将四种复制的聚糖线性组合，发现聚糖评分与高血压、收缩压和舒张压相关。我们的结果表明 IgG 糖组在高血压发生之前发生变化。
Glycosylation of immunoglobulin G (IgG) is an important regulator of the immune system and has been implicated in prevalent hypertension.The aim of this study is to investigate whether the IgG glycome begins to change prior to hypertension diagnosis by analysing the IgG glycome composition in a large population-based female cohort with 2 independent replication samples. We included 989 unrelated cases with incident hypertension and 1628 controls from the TwinsUK cohort (mean follow-up time of 6.3 years) with IgG measured at baseline by ultra-performance liquid chromatography and longitudinal BP measurement available. We replicated our findings in 106 individuals from the 10 001 Dalmatians and 729 from KORA S4. Cox regression mixed models were applied to identify changes in glycan traits pre-incident hypertension, after adjusting for age, mean arterial pressure, body mass index, family relatedness and multiple testing (FDR < 0.1). Significant IgG-incident hypertension associations were replicated in the two independent cohorts by leveraging Cox regression mixed models in the 10 001 Dalmatians and logistic regression models in the KORA cohort. We identified and replicated 4 glycan traits, incidence of bisecting GlcNAc, GP4, GP9 and GP21, that are predictive of incident hypertension after adjusting for confoundes and multiple testing (HR[95%CI] ranging from 0.45[0.24;0.84] for GP21 to 2.9[1.5;5.68]) for GP4). We then linearly combined the four replicated glycans and found that the glycan score correlated with incident hypertension, SBP and DBP. Our results suggest that the IgG glycome changes prior to the development of hypertension.