PMID- 29535164
OWN - NLM
STAT- In-Data-Review
LR  - 20190329
IS  - 1524-4571 (Electronic)
IS  - 0009-7330 (Linking)
VI  - 122
IP  - 11
DP  - 2018 May 25
TI  - Glycosylation Profile of Immunoglobulin G Is Cross-Sectionally Associated With
      Cardiovascular Disease Risk Score and Subclinical Atherosclerosis in Two
      Independent Cohorts.
PG  - 1555-1564
LID - 10.1161/CIRCRESAHA.117.312174 [doi]
AB  - RATIONALE: One measure of protein glycosylation (GlycA) has been reported to
      predict higher cardiovascular risk by reflecting inflammatory pathways.
      OBJECTIVE: The main objective of this study is to assess the role of a
      comprehensive panel of IgG glycosylation traits on traditional risk factors for
      cardiovascular disease and on presence of subclinical atherosclerosis in addition
      to GlycA. METHODS AND RESULTS: We measured 76 IgG glycosylation traits in 2970
      women (age range, 40-79 years) from the TwinsUK cohort and correlated it to their
      estimated 10-year atherosclerotic cardiovascular disease risk score and their
      carotid and femoral plaque measured by ultrasound imaging. Eight IgG glycan
      traits are associated with the 10-year atherosclerotic cardiovascular disease
      risk score after adjusting for multiple tests and for individual risk factors-5
      with increased risk and 3 with decreased risk. These glycans replicated in 967
      women from ORCADES cohort (Orkney Complex Disease Study), and 6 of them were also
      associated in 845 men. A linear combination of IgG glycans and GlycA is also
      associated with presence of carotid (odds ratio, 1.55; 95% confidence interval,
      1.25-1.93; P=7.5x10(-5)) and femoral (odds ratio, 1.32; 95% confidence interval, 
      1.06-1.64; P=0.01) plaque in a subset of women with atherosclerosis data after
      adjustment for traditional risk factors. One specific glycosylation trait,
      GP18-the percentage of FA2BG2S1 glycan in total IgG glycans, was negatively
      correlated with very-low-density lipoprotein and triglyceride levels in serum and
      with presence of carotid plaque (odds ratio, 0.60; 95% confidence interval,
      0.50-0.71; P=5x10(-4)). CONCLUSIONS: We find molecular pathways linking IgG to
      arterial lesion formation. Glycosylation traits are independently associated with
      subclinical atherosclerosis. One specific trait related to the sialylated
      N-glycan is negatively correlated with cardiovascular disease risk,
      very-low-density lipoprotein and triglyceride serum levels, and presence of
      carotid plaque.
CI  - (c) 2018 The Authors.
FAU - Menni, Cristina
AU  - Menni C
AD  - From the Department of Twin Research and Genetic Epidemiology (C.M., M.M., J.Z., 
      T.D.S., A.M.V.).
FAU - Gudelj, Ivan
AU  - Gudelj I
AD  - King's College London, United Kingdom; Genos Glycoscience Research Laboratory,
      Zagreb, Croatia (I.G., I.T.-A., G.L.).
FAU - Macdonald-Dunlop, Erin
AU  - Macdonald-Dunlop E
AD  - Centre for Global Health Research, Usher Institute of Population Health Sciences 
      and Informatics (E.M.-D., P.K.J., J.F.W.).
FAU - Mangino, Massimo
AU  - Mangino M
AD  - From the Department of Twin Research and Genetic Epidemiology (C.M., M.M., J.Z., 
      T.D.S., A.M.V.).
AD  - University of Edinburgh, Scotland; National Institute for Health Research
      Biomedical Research Centre at Guy's and St Thomas' Foundation Trust, London, UK
      (M.M.).
FAU - Zierer, Jonas
AU  - Zierer J
AD  - From the Department of Twin Research and Genetic Epidemiology (C.M., M.M., J.Z., 
      T.D.S., A.M.V.).
AD  - Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum Munchen,
      Neuherberg, Germany (J.Z.).
FAU - Besic, Erim
AU  - Besic E
AD  - Faculty of Pharmacy and Biochemistry, University of Zagreb, Croatia (E.B., G.L.).
FAU - Joshi, Peter K
AU  - Joshi PK
AD  - Centre for Global Health Research, Usher Institute of Population Health Sciences 
      and Informatics (E.M.-D., P.K.J., J.F.W.).
FAU - Trbojevic-Akmacic, Irena
AU  - Trbojevic-Akmacic I
AD  - King's College London, United Kingdom; Genos Glycoscience Research Laboratory,
      Zagreb, Croatia (I.G., I.T.-A., G.L.).
FAU - Chowienczyk, Phil J
AU  - Chowienczyk PJ
AD  - Department of Clinical Pharmacology, British Heart Foundation Centre (P.J.C.).
FAU - Spector, Tim D
AU  - Spector TD
AD  - From the Department of Twin Research and Genetic Epidemiology (C.M., M.M., J.Z., 
      T.D.S., A.M.V.).
FAU - Wilson, James F
AU  - Wilson JF
AD  - Centre for Global Health Research, Usher Institute of Population Health Sciences 
      and Informatics (E.M.-D., P.K.J., J.F.W.).
AD  - Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular
      Medicine, Western General Hospital (J.F.W.).
FAU - Lauc, Gordan
AU  - Lauc G
AD  - King's College London, United Kingdom; Genos Glycoscience Research Laboratory,
      Zagreb, Croatia (I.G., I.T.-A., G.L.).
AD  - Faculty of Pharmacy and Biochemistry, University of Zagreb, Croatia (E.B., G.L.).
FAU - Valdes, Ana M
AU  - Valdes AM
AD  - From the Department of Twin Research and Genetic Epidemiology (C.M., M.M., J.Z., 
      T.D.S., A.M.V.) ana.valdes@nottingham.ac.uk.
AD  - School of Medicine, Nottingham City Hospital, United Kingdom (A.M.V.).
AD  - National Institute for Health Research (NIHR) Nottingham Biomedical Research
      Centre, United Kingdom (A.M.V.).
LA  - eng
GR  - Wellcome Trust/United Kingdom
GR  - MR/M016560/1/Medical Research Council/United Kingdom
GR  - SP/14/8/31352/British Heart Foundation/United Kingdom
PT  - Journal Article
DEP - 20180313
PL  - United States
TA  - Circ Res
JT  - Circulation research
JID - 0047103
PMC - PMC5970566
MID - EMS76590
OTO - NOTNLM
OT  - atherosclerosis
OT  - cardiovascular disease risk
OT  - glycosylation
OT  - immunoglobulin G
OT  - plaque, atherosclerotic
EDAT- 2018/03/15 06:00
MHDA- 2018/03/15 06:00
CRDT- 2018/03/15 06:00
PHST- 2017/10/03 00:00 [received]
PHST- 2018/02/27 00:00 [revised]
PHST- 2018/03/12 00:00 [accepted]
PHST- 2018/03/15 06:00 [pubmed]
PHST- 2018/03/15 06:00 [medline]
PHST- 2018/03/15 06:00 [entrez]
AID - CIRCRESAHA.117.312174 [pii]
AID - 10.1161/CIRCRESAHA.117.312174 [doi]
PST - ppublish
SO  - Circ Res. 2018 May 25;122(11):1555-1564. doi: 10.1161/CIRCRESAHA.117.312174. Epub
      2018 Mar 13.