Glycosylation of IgG Associates with Hypertension and Type 2 Diabetes Mellitus Comorbidity in the Chinese Muslim Ethnic Minorities and the Han Chinese.

Xiaoni Meng,Weijie Cao,Jerko Štambuk,Manshu Song,Xiuhua Guo,Marija Vilaj,Gordan Lauc,Di Liu,Hao Wang,Youxin Wang,Lijuan Wu,Jinxia Zhang,Mamatyusupu Dolikun,Ana Momčilović,Xingang Li,Jie Zhang,Deqiang Zheng,Wei Wang,Xiaoyu Zhang,Irena Trbojević‐Akmačić

doi:10.3390/jpm11070614

Abstract

Objectives: Hypertension and type 2 diabetes mellitus comorbidity (HDC) is common, which confers a higher risk of cardiovascular disease than the presence of either condition alone. Describing the underlying glycomic changes of immunoglobulin G (IgG) that predispose individuals to HDC may help develop novel protective immune-targeted and anti-inflammatory therapies. Therefore, we investigated glycosylation changes of IgG associated with HDC. Methods: The IgG N-glycan profiles of 883 plasma samples from the three northwestern Chinese Muslim ethnic minorities and the Han Chinese were analyzed by ultra-performance liquid chromatography instrument. Results: We found that 12 and six IgG N-glycan traits showed significant associations with HDC in the Chinese Muslim ethnic minorities and the Han Chinese, respectively, after adjustment for potential confounders and false discovery rate. Adding the IgG N-glycan traits to the baseline models, the area under the receiver operating characteristic curves (AUCs) of the combined models differentiating HDC from hypertension (HTN), type 2 diabetes mellitus (T2DM), and healthy individuals were 0.717, 0.747, and 0.786 in the pooled samples of Chinese Muslim ethnic minorities, and 0.828, 0.689, and 0.901 in the Han Chinese, respectively, showing improved discriminating performance than both the baseline models and the glycan-based models. Conclusion: Altered IgG N-glycan profiles were shown to associate with HDC, suggesting the involvement of inflammatory processes of IgG glycosylation. The alterations of IgG N-glycome, illustrated here for the first time in HDC, demonstrate a biomarker potential, which may shed light on future studies investigating their potential for monitoring or preventing the progression from HTN or T2DM towards HDC.

Highlights

Hypertension (HTN) is one of the leading modifiable risk factors for morbidity and mortality of cardiovascular disease (CVD) worldwide [1]
We investigated the changes in immunoglobulin G (IgG) N-glycosylation profiles associated with HTN and T2DM comorbidity (HDC) and their biomarker potential for distinguishing HDC from HTN, type 2 diabetes mellitus (T2DM), and healthy individuals in the aforementioned populations
In the pooling of the Chinese Muslim ethnic minorities, the age significantly differed in HDC compared to T2DM and healthy controls, and the systolic blood pressure (SBP) and diastolic blood pressure (DBP) were significantly higher in the HDC

Summary

Introduction

Hypertension (HTN) is one of the leading modifiable risk factors for morbidity and mortality of cardiovascular disease (CVD) worldwide [1]. Previous studies have shown that hypertension is at least twice as frequent in patients with diabetes compared with those who do not have diabetes [5]. A considerable portion of the world population undergoes coexistent T2DM and HTN, which increases the risk of CVD and renal failure in individuals [6]. Compared with the normotensive non-diabetic individuals, patients with HTN and T2DM comorbidity (HDC) have a four-fold increased risk of CVD [7]. The number of patients diagnosed with HTN and T2DM comorbidity (HDC) is on the rise, resulting in increased medical expenses and resource utilization [8]. Further studies of biomarkers for monitoring and preventing the progression from HTN or T2DM towards

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Discussion

Conclusion