Xiaoni Meng1, Manshu Song1,2, Marija Vilaj3, Jerko Štambuk3, Mamatyusupu Dolikun4, Jie Zhang1, Di Liu1, Hao Wang5, Xiaoyu Zhang1, Jinxia Zhang1, Weijie Cao1, Ana Momčilović3, Irena Trbojević-Akmačić3, Xingang Li2,6, Deqiang Zheng1, Lijuan Wu1, Xiuhua Guo1, Youxin Wang1,2, Gordan Lauc3,7, Wei Wang1,2,6. 1. Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing 100069, China. 2. School of Medical and Health Sciences, Edith Cowan University, Perth, WA 6027, Australia. 3. Genos Glycoscience Research Laboratory, 10000 Zagreb, Croatia. 4. College of the Life Sciences and Technology, Xinjiang University, Urumqi 830046, China. 5. Department of Clinical Epidemiology and Evidence-Based Medicine, National Clinical Research Center for Digestive Disease, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China. 6. Centre for Precision Health, Edith Cowan University, Perth, WA 6027, Australia. 7. Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia.
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.
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.
Entities:
Keywords:
IgG; N-glycosylation; biomarkers; hypertension and type 2 diabetes mellitus comorbidity
Authors: Jennifer E Huffman; Ana Knezevic; Veronique Vitart; Jayesh Kattla; Barbara Adamczyk; Mislav Novokmet; Wilmar Igl; Maja Pucic; Lina Zgaga; Åsa Johannson; Irma Redzic; Olga Gornik; Tatijana Zemunik; Ozren Polasek; Ivana Kolcic; Marina Pehlic; Carolien A M Koeleman; Susan Campbell; Sarah H Wild; Nicholas D Hastie; Harry Campbell; Ulf Gyllensten; Manfred Wuhrer; James F Wilson; Caroline Hayward; Igor Rudan; Pauline M Rudd; Alan F Wright; Gordan Lauc Journal: Hum Mol Genet Date: 2011-09-09 Impact factor: 6.150