title: Effects of statins on the immunoglobulin G glycome.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Even if the association between IgG N-glycome and statins exists, it is not large enough to pose a problem for glycomic studies.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Zagreb, Faculty of Pharmacy and Biochemistry, Zagreb, Croatia.
authors.forename: Toma
authors.initials: T
authors.lastname: Keser
authors.affiliation: Genos Glycoscience Research Laboratory, Zagreb, Croatia.
authors.forename: Frano
authors.initials: F
authors.lastname: Vučković
authors.affiliation: 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.
authors.forename: Clara
authors.initials: C
authors.lastname: Barrios
authors.affiliation: 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.
authors.forename: Jonas
authors.initials: J
authors.lastname: Zierer
authors.affiliation: 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.
authors.forename: Annika
authors.initials: A
authors.lastname: Wahl
authors.affiliation: Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Akintunde O
authors.initials: AO
authors.lastname: Akinkuolie
authors.affiliation: Genos Glycoscience Research Laboratory, Zagreb, Croatia.
authors.forename: Jerko
authors.initials: J
authors.lastname: Štambuk
authors.affiliation: Laboratory of Prion Biology, Department of Neuroscience, Scuola Internazionale Superiore di Studi Avanzati (SISSA), Trieste, Italy.
authors.forename: Natali
authors.initials: N
authors.lastname: Nakić
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Zagreb, Faculty of Pharmacy and Biochemistry, Zagreb, Croatia.
authors.forename: Tamara
authors.initials: T
authors.lastname: Pavić
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Zagreb, Faculty of Pharmacy and Biochemistry, Zagreb, Croatia.
authors.forename: Josipa
authors.initials: J
authors.lastname: Periša
authors.affiliation: Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Samia
authors.initials: S
authors.lastname: Mora
authors.affiliation: 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.
authors.forename: Christian
authors.initials: C
authors.lastname: Gieger
authors.affiliation: Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
authors.forename: Cristina
authors.initials: C
authors.lastname: Menni
authors.affiliation: Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
authors.forename: Tim D
authors.initials: TD
authors.lastname: Spector
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Zagreb, Faculty of Pharmacy and Biochemistry, Zagreb, Croatia.
authors.forename: Olga
authors.initials: O
authors.lastname: Gornik
authors.affiliation: 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.
authors.forename: Gordan
authors.initials: G
authors.lastname: Lauc
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism; D000368:Aged; D004311:Double-Blind Method; D005260:Female; D054794:Glycomics / Q000379:methods; D006031:Glycosylation / Q000187:drug effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects*; D007074:Immunoglobulin G / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011134:Polysaccharides / Q000378:metabolism*; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D013449:Sulfonamides / Q000378:metabolism; D006023:Glycoproteins
chemical_list: D000117:Acetylglucosamine; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007074:Immunoglobulin G; D011134:Polysaccharides; D013449:Sulfonamides; C046179:glycosylated IgG; D006023:Glycoproteins
keywords: Immunoglobulin G; N-glycosylation; Rosuvastatin; Statin; Total plasma N-glycome