Abstract

BackgroundStatins 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. MethodsThe 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. ResultsIn 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. ConclusionsIn 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 significanceEven if the association between IgG N-glycome and statins exists, it is not large enough to pose a problem for glycomic studies.

Highlights

  • Glycosylation is a complex, highly specific and regulated co- and post-translational process that covalently links glycans to proteins and lipids [1,2]

  • The association between statin use and FA2B was replicated in the KORA cohort

  • In the TwinsUK and KORA cohorts, statin use was associated with a small increase of pro-inflammatory Immunoglobulin G (IgG) glycan, this finding was not confirmed in a subset of participants from the JUPITER trial

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Summary

Introduction

Glycosylation is a complex, highly specific and regulated co- and post-translational process that covalently links glycans (complex oligosaccharides) to proteins and lipids [1,2]. Structural variations in the attached glycans strongly affect structure and function of proteins. Structural differences in terminal glycan antennae is common and recent studies demonstrated significant variation in glycome composition both within and between individuals [5,6,7]. Glycosylation is age- and gender-specific but is affected by many environmental factors such as smoking, diet and medication [6,8,9,10]. In particular decrease in immunoglobulin G (IgG) galactosylation has been associated with adverse cardiometabolic risk factors, including: cholesterol, triglycerides, Creactive protein (CRP), HbA1c, insulin, glucose, body mass index (BMI) and kidney disease [13,14,15]. Immunoglobulin G (IgG) glycosylation has been associated with numerous cardiometabolic risk factors

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