Hyperuricemia is Associated with Immunoglobulin G N-Glycosylation: A Community-Based Study of Glycan Biomarkers

Abstract

The increasing prevalence of hyperuricemia has been recognized as an emerging public health concern in both developed and developing countries. Hyperuricemia is a metabolic condition characterized by an elevated serum uric acid, and associated with renal damage, diabetes, autoimmune disorders, and cardiovascular diseases. Although human genetic variation has been recognized as a factor, posttranslational cellular processes and glycan biomarkers have not been studied extensively for susceptibility to hyperuricemia. We evaluated whether immunoglobulin (Ig)G N-glycans play a role in hyperuricemia in the general population. This crosssectional study enrolled 635 participants (208 men and 427 women), ages ‡18 years, from a community-based population in Beijing, China. The IgG N-glycan composition of serum was analyzed by an ultraperformance liquid chromatography method. The prevalence of hyperuricemia observed in this sample was 5.98% (14.9% in men and 1.6% in women). Serum uric acid level was positively correlated with glycan peaks (GP)1, GP2, GP4, GP6, GP10, and GP11, whereas it was negatively correlated with GP12, GP13, GP14, GP15, GP18, and GP20. The combination of GP9, GP10, body mass index, and gender distinguished individuals with hyperuricemia from subjects without hyperuricemia, with an area under the curve value of 0.849 (95% confidence interval: 0.784-0.915). These findings collectively suggest a possible link between hyperuricemia and IgG N-glycans, which might be potentially mediated through inflammation-related mechanisms. Additional research on glycan biomarkers in independent and community-based population samples might allow the development of glycan diagnostics for hyperuricemia and gout in the future.

Profile of Immunoglobulin G N-Glycome in COVID-19 Patients: A Case-Control Study

“…Isolation of IgG and release of N -glycans were performed as described previously ( 21 , 22 ). Briefly, the frozen sera were thawed, and were centrifugated at 80 g for 10 min.…”

“…Then, it was centrifuged at 134 g for 5 min and 20 µl of the labeled N-glycans was loaded into the UPLC instruments. The glycans were analyzed with hydrophilic interaction liquid chromatography (HILIC) on a UPLC instrument (Walters Corporation, Milford, MA) ( 22 , 23 ). A total of 24 chromatographic glycan peaks (GPs 1–24) were identified as initial glycans.…”

“…Each glycan was quantified as relative values of the GP to total GPs. The glycan structure in each peak was matched as previously reported ( 22 ). We further calculated the derived glycans using the measurement data of the initial GPs, which consist of sialylation trait, bisecting GlcNAc trait, galactosylation trait, and fucosylation trait ( 11 ).…”

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

“…Unlike protein biosynthesis, glycans have no direct genetic templates. They are generated through intricate interactions among many genetic and environmental factors, and reflect the dynamic status of these factors (Adua et al, 2017;Hou et al, 2019;Liu et al, 2018b). These unique characteristics have received interest from the biomarker discovery and diagnostics research communities in relation to the possible role and potential use of N-glycans in complex diseases such as T2DM.…”

Knowledge Domain and Emerging Trends of IgG Glycosylation: A Bibliometric Study Based on CiteSpace

“…In recent years, people have conducted in-depth research on the glycosylation of various proteins, and clearly understand the important role of protein glycosylation in the occurrence and development of various diseases in humans [1][2][3][4][5][6] . People's interest in the research of immunoglobulin G (Ig G) glycosylation has increased dramatically, and many magazines have published a large number of articles on IgG glycosylation.…”