Defining the genetic control of human blood plasma N-glycome using genome-wide association study.
Chromatography, High Pressure Liquid
Cohort Studies
Fucosyltransferases
/ blood
Genome-Wide Association Study
Glucuronosyltransferase
/ blood
Glycosylation
Glycosyltransferases
/ genetics
Hepatocyte Nuclear Factor 1-alpha
/ blood
Humans
Immunoglobulin G
/ metabolism
Membrane Proteins
/ metabolism
Polymorphism, Genetic
Polysaccharides
/ blood
Quantitative Trait Loci
Journal
Human molecular genetics
ISSN: 1460-2083
Titre abrégé: Hum Mol Genet
Pays: England
ID NLM: 9208958
Informations de publication
Date de publication:
15 06 2019
15 06 2019
Historique:
received:
03
08
2018
revised:
01
03
2019
accepted:
06
03
2019
entrez:
5
6
2019
pubmed:
5
6
2019
medline:
7
2
2020
Statut:
ppublish
Résumé
Glycosylation is a common post-translational modification of proteins. Glycosylation is associated with a number of human diseases. Defining genetic factors altering glycosylation may provide a basis for novel approaches to diagnostic and pharmaceutical applications. Here we report a genome-wide association study of the human blood plasma N-glycome composition in up to 3811 people measured by Ultra Performance Liquid Chromatography (UPLC) technology. Starting with the 36 original traits measured by UPLC, we computed an additional 77 derived traits leading to a total of 113 glycan traits. We studied associations between these traits and genetic polymorphisms located on human autosomes. We discovered and replicated 12 loci. This allowed us to demonstrate an overlap in genetic control between total plasma protein and IgG glycosylation. The majority of revealed loci contained genes that encode enzymes directly involved in glycosylation (FUT3/FUT6, FUT8, B3GAT1, ST6GAL1, B4GALT1, ST3GAL4, MGAT3 and MGAT5) and a known regulator of plasma protein fucosylation (HNF1A). However, we also found loci that could possibly reflect other more complex aspects of glycosylation process. Functional genomic annotation suggested the role of several genes including DERL3, CHCHD10, TMEM121, IGH and IKZF1. The hypotheses we generated may serve as a starting point for further functional studies in this research area.
Identifiants
pubmed: 31163085
pii: 5374524
doi: 10.1093/hmg/ddz054
pmc: PMC6664388
doi:
Substances chimiques
DERL3 protein, human
0
HNF1A protein, human
0
Hepatocyte Nuclear Factor 1-alpha
0
Immunoglobulin G
0
Membrane Proteins
0
Polysaccharides
0
glycosylated IgG
0
Glycosyltransferases
EC 2.4.-
Fucosyltransferases
EC 2.4.1.-
galactosylgalactoylxylosylprotein 3-beta-glucuronosyltransferase
EC 2.4.1.135
Glucuronosyltransferase
EC 2.4.1.17
FUT6 protein, human
EC 2.4.1.65
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2062-2077Subventions
Organisme : Cancer Research UK
ID : 12076
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0600329
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/R026408/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0600237
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00007/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_U127527198
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_U127527198
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/K018647/1
Pays : United Kingdom
Organisme : Worldwide Cancer Research
ID : 12-1087
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00007/10
Pays : United Kingdom
Informations de copyright
© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
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