Toma Keser1, Frano Vučković2, Clara Barrios3, Jonas Zierer4, Annika Wahl5, Akintunde O Akinkuolie6, Jerko Štambuk2, Natali Nakić7, Tamara Pavić1, Josipa Periša1, Samia Mora6, Christian Gieger5, Cristina Menni8, Tim D Spector8, Olga Gornik1, Gordan Lauc9. 1. Department of Biochemistry and Molecular Biology, University of Zagreb, Faculty of Pharmacy and Biochemistry, Zagreb, Croatia. 2. Genos Glycoscience Research Laboratory, Zagreb, Croatia. 3. Department of Twin Research and Genetic Epidemiology, King's College London, London, UK; Department of Nephrology, Hospital del Mar, Institut Mar d'Investigacions Mediques, Barcelona, Spain. 4. Department of Twin Research and Genetic Epidemiology, King's College London, London, UK; Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany. 5. Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany. 6. Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. 7. Laboratory of Prion Biology, Department of Neuroscience, Scuola Internazionale Superiore di Studi Avanzati (SISSA), Trieste, Italy. 8. Department of Twin Research and Genetic Epidemiology, King's College London, London, UK. 9. Department of Biochemistry and Molecular Biology, University of Zagreb, Faculty of Pharmacy and Biochemistry, Zagreb, Croatia; Genos Glycoscience Research Laboratory, Zagreb, Croatia. Electronic address: glauc@pharma.hr.
Abstract
BACKGROUND:Statins are among the most widely prescribed medications worldwide and usually many individuals involved in clinical and population studies are on statin therapy. Immunoglobulin G (IgG) glycosylation has been associated with numerous cardiometabolic risk factors. METHODS: The aim of this study was to investigate the possible association of statin use with N-glycosylation of IgG. The association was analyzed in two large population cohorts (TwinsUK and KORA) using hydrophilic interaction liquid chromatography (HILIC-UPLC) in the TwinsUK cohort and reverse phase liquid chromatography coupled with electrospray mass spectrometry (LC-ESI-MS) in the KORA cohort. Afterwards we investigated the same association for only one statin (rosuvastatin) in a subset of individuals from the randomized double-blind placebo-controlled JUPITER study using LC-ESI-MS for IgG glycome and HILIC-UPLC for total plasma N-glycome. RESULTS: In the TwinsUK population, the use of statins was associated with higher levels of core-fucosylated biantennary glycan structure with bisecting N-acetylglucosamine (FA2B) and lower levels of core-fucosylated biantennary digalactosylated monosialylated glycan structure (FA2G2S1). The association between statin use and FA2B was replicated in the KORA cohort. In the JUPITER trial we found no statistically significant differences between the randomly allocated placebo and rosuvastatin groups. CONCLUSIONS: In the TwinsUK and KORA cohorts, statin use was associated with a small increase of pro-inflammatory IgG glycan, although this finding was not confirmed in a subset of participants from the JUPITER trial. GENERAL SIGNIFICANCE: Even if the association between IgG N-glycome and statins exists, it is not large enough to pose a problem for glycomic studies. Crown
RCT Entities:
BACKGROUND: Statins are among the most widely prescribed medications worldwide and usually many individuals involved in clinical and population studies are on statin therapy. Immunoglobulin G (IgG) glycosylation has been associated with numerous cardiometabolic risk factors. METHODS: The aim of this study was to investigate the possible association of statin use with N-glycosylation of IgG. The association was analyzed in two large population cohorts (TwinsUK and KORA) using hydrophilic interaction liquid chromatography (HILIC-UPLC) in the TwinsUK cohort and reverse phase liquid chromatography coupled with electrospray mass spectrometry (LC-ESI-MS) in the KORA cohort. Afterwards we investigated the same association for only one statin (rosuvastatin) in a subset of individuals from the randomized double-blind placebo-controlled JUPITER study using LC-ESI-MS for IgG glycome and HILIC-UPLC for total plasma N-glycome. RESULTS: In the TwinsUK population, the use of statins was associated with higher levels of core-fucosylated biantennary glycan structure with bisecting N-acetylglucosamine (FA2B) and lower levels of core-fucosylated biantennary digalactosylated monosialylated glycan structure (FA2G2S1). The association between statin use and FA2B was replicated in the KORA cohort. In the JUPITER trial we found no statistically significant differences between the randomly allocated placebo and rosuvastatin groups. CONCLUSIONS: In the TwinsUK and KORA cohorts, statin use was associated with a small increase of pro-inflammatory IgG glycan, although this finding was not confirmed in a subset of participants from the JUPITER trial. GENERAL SIGNIFICANCE: Even if the association between IgG N-glycome and statins exists, it is not large enough to pose a problem for glycomic studies. Crown
Authors: Jennifer E Huffman; Ana Knezevic; Veronique Vitart; Jayesh Kattla; Barbara Adamczyk; Mislav Novokmet; Wilmar Igl; Maja Pucic; Lina Zgaga; Åsa Johannson; Irma Redzic; Olga Gornik; Tatijana Zemunik; Ozren Polasek; Ivana Kolcic; Marina Pehlic; Carolien A M Koeleman; Susan Campbell; Sarah H Wild; Nicholas D Hastie; Harry Campbell; Ulf Gyllensten; Manfred Wuhrer; James F Wilson; Caroline Hayward; Igor Rudan; Pauline M Rudd; Alan F Wright; Gordan Lauc Journal: Hum Mol Genet Date: 2011-09-09 Impact factor: 6.150
Authors: Maja Pucić; Ana Knezević; Jana Vidic; Barbara Adamczyk; Mislav Novokmet; Ozren Polasek; Olga Gornik; Sandra Supraha-Goreta; Mark R Wormald; Irma Redzić; Harry Campbell; Alan Wright; Nicholas D Hastie; James F Wilson; Igor Rudan; Manfred Wuhrer; Pauline M Rudd; Djuro Josić; Gordan Lauc Journal: Mol Cell Proteomics Date: 2011-06-08 Impact factor: 5.911
Authors: Ana Knezević; Ozren Polasek; Olga Gornik; Igor Rudan; Harry Campbell; Caroline Hayward; Alan Wright; Ivana Kolcic; Niaobh O'Donoghue; Jonathan Bones; Pauline M Rudd; Gordan Lauc Journal: J Proteome Res Date: 2009-02 Impact factor: 4.466
Authors: Frano Vučković; Jasminka Krištić; Ivan Gudelj; Maria Teruel; Toma Keser; Marija Pezer; Maja Pučić-Baković; Jerko Štambuk; Irena Trbojević-Akmačić; Clara Barrios; Tamara Pavić; Cristina Menni; Youxin Wang; Yong Zhou; Liufu Cui; Haicheng Song; Qiang Zeng; Xiuhua Guo; Bernardo A Pons-Estel; Paul McKeigue; Alan Leslie Patrick; Olga Gornik; Tim D Spector; Miroslav Harjaček; Marta Alarcon-Riquelme; Mariam Molokhia; Wei Wang; Gordan Lauc Journal: Arthritis Rheumatol Date: 2015-11 Impact factor: 10.995
Authors: Evropi Theodoratou; Kujtim Thaçi; Felix Agakov; Maria N Timofeeva; Jerko Štambuk; Maja Pučić-Baković; Frano Vučković; Peter Orchard; Anna Agakova; Farhat V N Din; Ewan Brown; Pauline M Rudd; Susan M Farrington; Malcolm G Dunlop; Harry Campbell; Gordan Lauc Journal: Sci Rep Date: 2016-06-15 Impact factor: 4.379
Authors: Florent Clerc; Karli R Reiding; Bas C Jansen; Guinevere S M Kammeijer; Albert Bondt; Manfred Wuhrer Journal: Glycoconj J Date: 2015-11-10 Impact factor: 2.916
Authors: J N Liu; M Dolikun; J Štambuk; I Trbojević-Akmačić; J Zhang; H Wang; D Q Zheng; X Y Zhang; H L Peng; Z Y Zhao; D Liu; Y Sun; Q Sun; Q H Li; J X Zhang; M Sun; W J Cao; A Momčilović; G Razdorov; L J Wu; A Russell; Y X Wang; M S Song; G Lauc; W Wang Journal: J Hum Hypertens Date: 2018-06-05 Impact factor: 3.012
Authors: Shaza B Zaghlool; Dennis O Mook-Kanamori; Sara Kader; Nisha Stephan; Anna Halama; Rudolf Engelke; Hina Sarwath; Eman K Al-Dous; Yasmin A Mohamoud; Werner Roemisch-Margl; Jerzy Adamski; Gabi Kastenmüller; Nele Friedrich; Alessia Visconti; Pei-Chien Tsai; Tim Spector; Jordana T Bell; Mario Falchi; Annika Wahl; Melanie Waldenberger; Annette Peters; Christian Gieger; Marija Pezer; Gordan Lauc; Johannes Graumann; Joel A Malek; Karsten Suhre Journal: Hum Mol Genet Date: 2018-03-15 Impact factor: 6.150
Authors: Sunny S Singh; Annemieke Naber; Viktoria Dotz; Emma Schoep; Elham Memarian; Roderick C Slieker; Petra J M Elders; Gerda Vreeker; Simone Nicolardi; Manfred Wuhrer; Eric J G Sijbrands; Aloysius G Lieverse; Leen M 't Hart; Mandy van Hoek Journal: BMJ Open Diabetes Res Care Date: 2020-07
Authors: Domagoj Kifer; Panayiotis Louca; Ana Cvetko; Helena Deriš; Ana Cindrić; Harald Grallert; Annette Peters; Ozren Polašek; Olga Gornik; Massimo Mangino; Tim D Spector; Ana M Valdes; Sandosh Padmanabhan; Christian Gieger; Gordan Lauc; Cristina Menni Journal: J Hypertens Date: 2021-12-01 Impact factor: 4.776