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The association between subclass-specific IgG Fc N-glycosylation profiles and hypertension in the Uygur, Kazak, Kirgiz, and Tajik populations

Abstract

Hypertension results from the interaction of genetic and acquired factors. IgG occurs in the form of different subclasses, of which the effector functions show significant variation. The detailed differences between the glycosylation profiles of the individual IgG subclasses may be lost in a profiling method for total IgG N-glycosylation. In this study, subclass-specific IgG Fc glycosylation profile was investigated in the four northwestern Chinese minority populations, namely, Uygur (UIG), Kazak (KZK), Kirgiz (KGZ), and Tajik (TJK), composed of 274 hypertensive patients and 356 healthy controls. The results showed that ten directly measured IgG N-glycan traits (i.e., IgG1G0F, IgG2G0F, IgG2G1FN, IgG2G1FS, IgG2G2S, IgG4G0F, IgG4G1FS, IgG4G1S, IgG4G2FS, and IgG4G2N) representing galactosylation and sialylation are significantly associated with hypertension, with IgG4 consistently showing weaker associations of its sialylation, across the four ethnic groups. We observed a modest improvement on the AUC of ROC curve when the IgG Fc N-glycan traits are added into the glycan-based model (difference between AUCs, 0.044, 95% CI: 0.016–0.072, P = 0.002). The AUC of the diagnostic model indicated that the subclass-specific IgG Fc N-glycan profiles provide more information reinforcing current models utilizing age, gender, BMI, and ethnicity, and demonstrate the potential of subclass-specific IgG Fc N-glycosylation profiles to serve as a biomarker for hypertension. Further research is however required to determine the additive value of subclass-specific IgG Fc N-glycosylation on top of biomarkers, which are currently used.

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Acknowledgements

This study was supported by the National Natural Science Foundation of China (81573215, 31460285, and 81370083), Australian National Health and Medical Research Council (NH&MRC-APP1046711). Genos has received funding from European Commission FP7 grants MIMOmics (contract #305280), HTP-GlycoMet (contract #324400) and PainOmics (contract #602736), and H2020 grants GlySign (contract #722095), GlyCoCan (contract #676412), SYSCID (contract #733100), and IMforFuture (contract #721815) as well as funding from the European Structural and Investments funds for projects “New generation of high througput glycoanalytical services (contract #KK.01.2.1.01.0003) and “Croatian National Centre of Research Excellence in Personalized Healthcare” (contract #KK.01.1.1.01.0010). HW was supported by China Scholarship Council (CSC No. 201708110200). The authors thank the directors and relevant staff of relevant Health Bureaus for their support for recruiting the Uygur, Kazak, Kirgiz, and Tajik participants, and these volunteers and community leaders for their participation and support.

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Correspondence to YX Wang or MS Song.

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Conflict of interest

G. Lauc is the founder and owner of Genos Ltd, a private research organization that specializes in high-throughput glycomic analysis and has several patents in this field. J. Štambuk, I. Trbojević-Akmačić, A. Momčilović and G. Razdorov are employees of Genos Ltd.

Electronic supplementary material

Characteristics of the study subjects in the four ethnic groups: Uygur, Kazak, Kirgiz and Tajik

41371_2018_71_MOESM2_ESM.xlsx

Directly measured subclass-specific IgG Fc N-glycome composition in hypertension patients and healthy controls for the four separate ethnic groups, and a pooled group of all four ethnic groups

41371_2018_71_MOESM3_ESM.xlsx

Derived subclass-specific IgG Fc N-glycome composition in hypertension patients and healthy controls for the four separate ethnic groups, and a pooled groups of all four ethnic groups 

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Liu, J., Dolikun, M., Štambuk, J. et al. The association between subclass-specific IgG Fc N-glycosylation profiles and hypertension in the Uygur, Kazak, Kirgiz, and Tajik populations. J Hum Hypertens 32, 555–563 (2018). https://doi.org/10.1038/s41371-018-0071-0

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