Domagoj Kifer1, Panayiotis Louca2, Ana Cvetko1, Helena Deriš3, Ana Cindrić3, Harald Grallert4,5, Annette Peters5,6,7, Ozren Polašek8, Olga Gornik1, Massimo Mangino2,9, Tim D Spector2, Ana M Valdes2,10, Sandosh Padmanabhan11, Christian Gieger4,5, Gordan Lauc1,3, Cristina Menni2. 1. Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia. 2. Department of Twin Research, Kings College London, London, UK. 3. Genos Glycoscience Research Laboratory, Zagreb, Croatia. 4. Research Unit of Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München Research Center for Environmental Health. 5. German Center for Diabetes Research (DZD). 6. Institute of Epidemiology, Helmholtz Zentrum München Research Center for Environmental Health. 7. LMU Munich, IBE-Chair of Epidemiology, Neuherberg, Germany. 8. Department of Public Health, University of Split, School of Medicine, Split, Croatia. 9. NIHR Biomedical Research Centre at Guy's and St Thomas' Foundation Trust, London. 10. Academic Rheumatology Clinical Sciences Building, Nottingham City Hospital, University of Nottingham, Nottingham. 11. University of Glasgow, Glasgow, Scotland, UK.
Abstract
OBJECTIVES: Glycosylation of immunoglobulin G (IgG) is an important regulator of the immune system and has been implicated in prevalent hypertension. The aim of this study is to investigate whether the IgG glycome begins to change prior to hypertension diagnosis by analysing the IgG glycome composition in a large population-based female cohort with two independent replication samples. METHODS: We included 989 unrelated cases with incident hypertension and 1628 controls from the TwinsUK cohort (mean follow-up time of 6.3 years) with IgG measured at baseline by ultra-performance liquid chromatography and longitudinal BP measurement available. We replicated our findings in 106 individuals from the 10 001 Dalmatians and 729 from KORA S4. Cox regression mixed models were applied to identify changes in glycan traits preincident hypertension, after adjusting for age, mean arterial pressure, BMI, family relatedness and multiple testing (FDR < 0.1). Significant IgG-incident hypertension associations were replicated in the two independent cohorts by leveraging Cox regression mixed models in the 10 001 Dalmatians and logistic regression models in the KORA cohort. RESULTS: We identified and replicated four glycan traits, incidence of bisecting GlcNAc, GP4, GP9 and GP21, that are predictive of incident hypertension after adjusting for confoundes and multiple testing [hazard ratio (95% CI) ranging from 0.45 (0.24-0.84) for GP21 to 2.9 (1.5-5.68) for GP4]. We then linearly combined the four replicated glycans and found that the glycan score correlated with incident hypertension, SBP and DBP. CONCLUSION: Our results suggest that the IgG glycome changes prior to the development of hypertension.
OBJECTIVES: Glycosylation of immunoglobulin G (IgG) is an important regulator of the immune system and has been implicated in prevalent hypertension. The aim of this study is to investigate whether the IgG glycome begins to change prior to hypertension diagnosis by analysing the IgG glycome composition in a large population-based female cohort with two independent replication samples. METHODS: We included 989 unrelated cases with incident hypertension and 1628 controls from the TwinsUK cohort (mean follow-up time of 6.3 years) with IgG measured at baseline by ultra-performance liquid chromatography and longitudinal BP measurement available. We replicated our findings in 106 individuals from the 10 001 Dalmatians and 729 from KORA S4. Cox regression mixed models were applied to identify changes in glycan traits preincident hypertension, after adjusting for age, mean arterial pressure, BMI, family relatedness and multiple testing (FDR < 0.1). Significant IgG-incident hypertension associations were replicated in the two independent cohorts by leveraging Cox regression mixed models in the 10 001 Dalmatians and logistic regression models in the KORA cohort. RESULTS: We identified and replicated four glycan traits, incidence of bisecting GlcNAc, GP4, GP9 and GP21, that are predictive of incident hypertension after adjusting for confoundes and multiple testing [hazard ratio (95% CI) ranging from 0.45 (0.24-0.84) for GP21 to 2.9 (1.5-5.68) for GP4]. We then linearly combined the four replicated glycans and found that the glycan score correlated with incident hypertension, SBP and DBP. CONCLUSION: Our results suggest that the IgG glycome changes prior to the development of hypertension.
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Authors: Valentina L Greto; Ana Cvetko; Tamara Štambuk; Cristina Menni; Alessandra Geremia; Carolina V Arancibia-Cárcamo; Gordan Lauc; Niall J Dempster; Domagoj Kifer; Helena Deriš; Ana Cindrić; Frano Vučković; Mario Falchi; Richard S Gillies; Jeremy W Tomlinson; Olga Gornik; Bruno Sgromo; Tim D Spector Journal: Int J Obes (Lond) Date: 2021-05-03 Impact factor: 5.095
Authors: Helena Deriš; Domagoj Kifer; Ana Cindrić; Tea Petrović; Ana Cvetko; Irena Trbojević-Akmačić; Ivana Kolčić; Ozren Polašek; Louise Newson; Tim Spector; Cristina Menni; Gordan Lauc Journal: iScience Date: 2022-02-10
Authors: Jerka Dumić; Ana Cvetko; Irena Abramović; Sandra Šupraha Goreta; Antonija Perović; Marina Njire Bratičević; Domagoj Kifer; Nino Sinčić; Olga Gornik; Marko Žarak Journal: Front Cardiovasc Med Date: 2022-03-14