Department of Biochemistry and Molecular Biology, University of Zagreb, Faculty of Pharmacy and Biochemistry, Zagreb, Croatia.
Genos Glycoscience Research Laboratory, Zagreb, Croatia.
Biochim Biophys Acta Gen Subj. 2017 May;1861(5 Pt A):1152-1158. doi: 10.1016/j.bbagen.2017.02.029. Epub 2017 Mar 2.
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.
他汀类药物是全球应用最广泛的药物之一，通常有许多参与临床和人群研究的个体正在接受他汀类药物治疗。免疫球蛋白 G（IgG）糖基化与许多心血管代谢危险因素有关。
本研究旨在探讨他汀类药物使用与 IgG N-糖基化之间的可能关联。在 TwinsUK 队列中使用亲水相互作用液相色谱（HILIC-UPLC），在 KORA 队列中使用反相液相色谱与电喷雾质谱联用（LC-ESI-MS），在 TwinsUK 和 KORA 两个大型人群队列中分析了这种关联。然后，我们使用 LC-ESI-MS 进行 IgG 聚糖分析和 HILIC-UPLC 进行总血浆 N-聚糖分析，在 JUPITER 研究的随机双盲安慰剂对照亚组中仅研究了一种他汀类药物（瑞舒伐他汀）的相同关联。
在 TwinsUK 人群中，他汀类药物的使用与具有双分支 N-乙酰葡萄糖胺（FA2B）的核心岩藻糖基化双天线聚糖结构的更高水平以及核心岩藻糖基化双天线二半乳糖基单唾液酸化聚糖结构（FA2G2S1）的更低水平相关。他汀类药物使用与 FA2B 之间的关联在 KORA 队列中得到了复制。在 JUPITER 试验中，我们未发现随机分配的安慰剂和瑞舒伐他汀组之间存在统计学上显著差异。
在 TwinsUK 和 KORA 队列中，他汀类药物的使用与促炎 IgG 聚糖的小幅度增加相关，尽管在 JUPITER 试验的亚组参与者中未证实这一发现。
即使 IgG N-聚糖与他汀类药物之间存在关联，其程度也不足以对聚糖研究构成问题。
