Immunoglobulin GN-Glycans as Potential Postgenomic Biomarkers for Hypertension in the Kazakh Population

Abstract

Next-generation (postgenomic) biomarkers from the nascent field of glycomics now offer fresh vistas for innovation in chronic disease biomarkers and system diagnostics in clinical medicine. Our previous work has shown an association between hypertension and immunoglobulin G (IgG) glycome composition, suggesting that individual variation in N-glycosylation of IgG might contribute to hypertension pathogenesis. The present study examined, for the first time to the best of our knowledge, the IgG N-glycans as potential biomarkers for hypertension in the Kazakh population. The profile of 60 N-glycopeptides of IgG subclass isolated from plasma samples of 150 Kazakh study participants was analyzed by nano ultra-performance liquid chromatography with mass spectrometry. Fourteen IgG subclass-specific Fc N-glycopeptide structures, along with one derived glycosylation trait in subclasses IgG2/3 and IgG4, were found to correlate with systolic blood pressure and/or diastolic blood pressure. For differentiation of hypertension and healthy status in the Kazakh population sample, the receiver operating characteristic curve analysis showed that the performance of the model, including nine IgG N-glycans, was greater than the traditional gender, age, and body mass index based model (p < 0.05). This study indicates that alteration in Fc N-glycopeptide profiles of plasma IgG subclasses is associated with blood pressure status in the Kazakh population. IgG N-glycosylation profiles may serve as potential biomarkers for hypertension in the Kazakhs, thus contributing to move toward personalized medicine. Further studies of postgenomic glycomic biomarkers in cardiovascular and chronic diseases are timely and called for.

Type 2 Diabetes Mellitus is Associated with the Immunoglobulin G N-Glycome through Putative Proinflammatory Mechanisms in an Australian Population

“…Glycome reflects the real-time status of these intricate interplays and promises potential biomarkers for multifactorial diseases. Consistent with previous studies on IgG N-glycome and total N-glycome (Gao et al, 2017;Ge et al, 2018;Lemmers et al, 2017;Liu et al, 2018a;Lu et al, 2011;Russell et al, 2017Russell et al, , 2018bWang et al, 2016b;Yu et al, 2016), in this study, the IgG N-glycan traits were identified as significantly associated with age, sex, BMI, blood pressure, blood lipids, FBG, and HbA1c.…”

“…Similar conclusions were also reached in studies of IgG Nglycome on chronological aging in different populations Yu et al, 2016) and hypertension in different nations from one population (Gao et al, 2017;Wang et al, 2016b). The inconsistency of significantly different glycans seen between our results and those of previous studies shows the diversity of T2DM among populations in glycome level.…”

“…Immunoglobulin G (IgG) plays a key role in the human immune system and accounts for 75-85% of total Ig in human plasma (Mescher, 2016). The IgG N-glycomic alterations have been connected to several of T2DM's clinical risk factors, including aging (Yu et al, 2016), body mass index (BMI) (Perkovic et al, 2014), central adiposity , hypertension (Gao et al, 2017;Liu et al, 2018c;Wang et al, 2016b), and dyslipidemia (Liu et al, 2018a).…”

Next-Generation (Glycomic) Biomarkers for Cardiometabolic Health: A Community-Based Study of Immunoglobulin G N-Glycans in a Chinese Han Population

“…Previous glycomics research has shown that IgG Nglycans are associated with the cardiometabolic risk factors, including hypertension (Gao et al, 2017;Liu et al, 2018c;Wang et al, 2016b), T2DM (Ge et al, 2018;Lemmers et al, 2017), central obesity (Russell et al, 2018), and dyslipidemia (Liu et al, 2018a). In this study, we described the association of IgG N-glycans with the 15 cardiometabolic risk factors in a Chinese Han population.…”

“…N-glycans attach to the conserved asparagine 297 of both heavy chains in the fragment crystallizable region of IgG and act as a switch between proinflammatory and anti-inflammatory responses of IgG (Gornik et al, 2012;Jefferis, 2009). Changes to the IgG Nglycan profiles are involved in several inflammatory diseases, such as hypertension (Gao et al, 2017;Liu et al, 2018c;Wang et al, 2016b), stroke (Liu et al, 2018b), T2DM (Ge et al, 2018;Lemmers et al, 2017), Parkinson's disease , and rheumatoid arthritis (Sebastian et al, 2016).…”