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

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

doi:10.3390/jpm11070614

Cited by 14 publications

(7 citation statements)

References 46 publications

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“…Hypertension and diabetes are risk factors for the development of severe cardiovascular disease and are prevalent comorbidities [1][2][3][4][5][6][7][8][9][10][11]. The causal relationship between hypertension and diabetes is not clear.…”

Section: Introductionmentioning

confidence: 99%

Risk factors for hypertension and diabetes comorbidity in a Korean population: A cross-sectional study

Hee

Lee

2022

PLoS ONE

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Background Hypertension and diabetes are risk factors for severe cardiovascular disease and are prevalent comorbidities. No studies have examined the associations of various risk factors related to anthropometry, bone mineral density and body composition of specific body regions with hypertension and diabetes comorbidity (HDC). This study explored the association between HDC and various risk factors related to specific body regions. Method A total of 7,978 subjects (3,451 men and 4,527 women) aged ≥ 50 years were included in the analysis. A binary logistic regression analysis based on complex sample data analysis was conducted to examine associations between the normal and diabetes groups, between the normal and hypertension groups, and between the normal and HDC groups. Results Among Korean adults aged ≥ 50 years, 11.27% of men and 10.05% of women had both diabetes and hypertension. The HDC prevalence was higher in men than in women. In men, waist-to-height ratio (WHtR, adjusted OR = 1.63 [1.22–2.18], adjusted p<0.001) exhibited a more significant association with HDC than other indices, left leg fat mass (adjusted OR = 0.61 [0.45–0.81], adjusted p = 0.0009) and right leg fat mass (adjusted OR = 0.60 [0.45–0.81], adjusted p = 0.0007) displayed strong negative associations with diabetes, and left leg lean mass (adjusted OR = 0.77 [0.67–0.89], adjusted p = 0.0002) and trunk fat mass (adjusted OR = 1.28 [1.07–1.52], adjusted p = 0.0062) were significantly associated with hypertension. In women, left leg fat mass (adjusted OR = 0.29 [0.22–0.39], adjusted p<0.0001) and right leg fat mass (adjusted OR = 0.32 [0.23–0.45], adjusted p<0.0001) exhibited strong negative associations with HDC, waist circumference (WC) (adjusted OR = 2.15 [1.40–3.30], adjusted p = 0.0005) showed a stronger association with diabetes than did other indices, and WC (adjusted OR = 1.39 [1.11–1.74], adjusted p = 0.0040) and WHtR (adjusted OR = 1.39 [1.09–1.76], adjusted p = 0.0075) were significantly associated with hypertension. Discussion HDC was more strongly associated with fat and lean mass than diabetes and hypertension. The association between HDC and body fat variables was more robust in women than in men.

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Section: Introductionmentioning

confidence: 99%

Risk factors for hypertension and diabetes comorbidity in a Korean population: A cross-sectional study

Hee

Lee

2022

PLoS ONE

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“…7,8 The phenotype of glycans in healthy individuals is stable but can dramatically change under pathological conditions, such as inflammation and hypertension. 9,10 IgG, the most abundant glycoprotein in human biofluids and the main effector of the humoral immune system, is involved in inflammatory pathways and regulates systemic inflammatory homeostasis at multiple levels, primarily through its N-glycans. [11][12][13][14] The anti-and proinflammatory activities of IgG can be completely altered by its N-glycans.…”

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confidence: 99%

Human Plasma IgG N -Glycome Profiles Reveal a Proinflammatory Phenotype in Chronic Thromboembolic Pulmonary Hypertension

et al. 2023

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BACKGROUND: The pathological mechanism of chronic thromboembolic pulmonary hypertension (CTEPH) is not fully understood, and inflammation has been reported to be one of its etiological factors. IgG regulates systemic inflammatory homeostasis, primarily through its N -glycans. Little is known about IgG N -glycosylation in CTEPH. We aimed to map the IgG N -glycome of chronic thromboembolic pulmonary hypertension to provide new insights into its pathogenesis and discover novel markers and therapies. METHODS: We characterized the plasma IgG N -glycome of patients with chronic thromboembolic pulmonary hypertension in a discovery cohort and validated our results in an independent validation cohort using matrix-assisted laser desorption/ionization time of flight mass spectrometry. Thereafter, we correlated IgG N -glycans with clinical parameters and circulating inflammatory cytokines in patients with CTEPH. Furthermore, we determined IgG N -glycan quantitative trait loci in chronic thromboembolic pulmonary hypertension to reveal partial mechanisms underlying glycan changes. RESULTS: Decreased IgG galactosylation representing a proinflammatory phenotype was found in CTEPH. The distribution of IgG galactosylation showed a strong association with NT-proBNP (N-terminal pro-B-type natriuretic peptide) in CTEPH. In line with the glycomic findings, IgG pro-/anti-inflammatory N -glycans correlated well with a series of inflammatory markers and gene loci that have been reported to be involved in the regulation of these glycans or inflammatory immune responses. CONCLUSIONS: This is the first study to reveal the full signature of the IgG N -glycome of a proinflammatory phenotype and the genes involved in its regulation in CTEPH. Plasma IgG galactosylation may be useful for evaluating the inflammatory state in patients with CTEPH; however, this requires further validation. This study improves our understanding of the mechanisms underlying chronic thromboembolic pulmonary hypertension inflammation from the perspective of glycomics.

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“…Twenty-seven N-glycan traits from IgG subclasses were associated with T2D in the Uyghur population [ 43 ]. In addition, a study of Chinese Muslim ethnicity and the Han population reported associations of IgG-glycans with hypertension and type 2 diabetes mellitus comorbidity [ 45 ]. A study of European samples developed a score based on significant IgG-GPs, which was associated with higher diabetes risk and was robust against confounder and clinical biomarkers [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Leveraging IgG N-glycosylation to infer the causality between T2D and hypertension

Wang

Cao

et al. 2023

Diabetol Metab Syndr

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Background Observational studies demonstrated a bidirectional association between type 2 diabetes (T2D) and hypertension, whereas Mendelian randomization (MR) analyses supported the causality from T2D to hypertension but not causal from hypertension to T2D. We previously found that IgG N-glycosylation is associated with both T2D and hypertension, and thus IgG N-glycosylation might link the causality between them. Methods We carried out a genome-wide association study (GWAS) to identify IgG N-glycosylation-quantitative-trait loci (QTLs) integrating GWAS for T2D and hypertension and then performed bidirectional univariable and multivariable MR analyses to infer the causal association among them. The inverse-variance-weighted (IVW) analysis was performed as the primary analysis, followed by some sensitivity analyses to explore the stability of the results. Results Six putatively causal IgG N-glycans for T2D and four for hypertension were identified in the IVW method. Genetically predicted T2D increased the risk of hypertension (odds ratio [OR] = 1.177, 95% confidence interval (95% CI) = 1.037–1.338, P = 0.012) and vice versa (OR = 1.391, 95% CI = 1.081–1.790, P = 0.010). Multivariable MR showed that T2D remained at risk effect with hypertension ([OR] = 1.229, 95% CI = 1.140–1.325, P = 7.817 × 10–8) after conditioning on T2D-related IgG-glycans. Conversely, hypertension was associated with higher T2D risk (OR = 1.287, 95% CI = 1.107–1.497, P = 0.001) after adjusting for related IgG-glycans. No evidence of horizontal pleiotropy was observed, as MR‒Egger regression provided P values for intercept > 0.05. Conclusion Our study validated the mutual causality between T2D and hypertension from the perspective of IgG N-glycosylation, further validating the “common soil” hypothesis underlying the pathogenesis of T2D and hypertension.

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

Cited by 14 publications

References 46 publications

Risk factors for hypertension and diabetes comorbidity in a Korean population: A cross-sectional study

Risk factors for hypertension and diabetes comorbidity in a Korean population: A cross-sectional study

Human Plasma IgG N -Glycome Profiles Reveal a Proinflammatory Phenotype in Chronic Thromboembolic Pulmonary Hypertension

Leveraging IgG N-glycosylation to infer the causality between T2D and hypertension

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