Genome-wide association study identifies two loci strongly affecting transferrin glycosylation.

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State: Public
Version: author
Serval ID
serval:BIB_4CBEDBD36408
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Genome-wide association study identifies two loci strongly affecting transferrin glycosylation.
Journal
Human molecular genetics
Author(s)
Kutalik Z., Benyamin B., Bergmann S., Mooser V., Waeber G., Montgomery G.W., Martin N.G., Madden P.A., Heath A.C., Beckmann J.S., Vollenweider P., Marques-Vidal P., Whitfield J.B.
ISSN
1460-2083 (Electronic)
ISSN-L
0964-6906
Publication state
Published
Issued date
15/09/2011
Peer-reviewed
Oui
Volume
20
Number
18
Pages
3710-3717
Language
english
Notes
Publication types: Journal Article ; Meta-Analysis ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Polysaccharide sidechains attached to proteins play important roles in cell-cell and receptor-ligand interactions. Variation in the carbohydrate component has been extensively studied for the iron transport protein transferrin, because serum levels of the transferrin isoforms asialotransferrin + disialotransferrin (carbohydrate-deficient transferrin, CDT) are used as biomarkers of excessive alcohol intake. We conducted a genome-wide association study to assess whether genetic factors affect CDT concentration in serum. CDT was measured in three population-based studies: one in Switzerland (CoLaus study, n = 5181) and two in Australia (n = 1509, n = 775). The first cohort was used as the discovery panel and the latter ones served as replication. Genome-wide single-nucleotide polymorphism (SNP) typing data were used to identify loci with significant associations with CDT as a percentage of total transferrin (CDT%). The top three SNPs in the discovery panel (rs2749097 near PGM1 on chromosome 1, and missense polymorphisms rs1049296, rs1799899 in TF on chromosome 3) were successfully replicated , yielding genome-wide significant combined association with CDT% (P = 1.9 × 10(-9), 4 × 10(-39), 5.5 × 10(-43), respectively) and explain 5.8% of the variation in CDT%. These allelic effects are postulated to be caused by variation in availability of glucose-1-phosphate as a precursor of the glycan (PGM1), and variation in transferrin (TF) structure.

Keywords
Adult, Aged, Aged, 80 and over, Alcohol Drinking/genetics, Cohort Studies, European Continental Ancestry Group/genetics, Female, Genome-Wide Association Study, Glycosylation, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Switzerland, Transferrin/analogs & derivatives, Transferrin/genetics, Transferrin/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
15/06/2011 14:00
Last modification date
20/08/2019 14:01
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