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

Kutalik, Zoltan, Benyamin, Beben, Bergmann, Sven, Mooser, Vincent, Waeber, Gerard, Montgomery, Grant W., Martin, Nicholas G., Madden, Pamela A. F., Heath, Andrew C., Beckmann, Jacques S., Vollenweider, Peter, Marques-Vidal, Pedro and Whitfield, John B. (2011) Genome-wide association study identifies two loci strongly affecting transferrin glycosylation. Human Molecular Genetics, 20 18: 3710-3717. doi:10.1093/hmg/ddr272

Author Kutalik, Zoltan
Benyamin, Beben
Bergmann, Sven
Mooser, Vincent
Waeber, Gerard
Montgomery, Grant W.
Martin, Nicholas G.
Madden, Pamela A. F.
Heath, Andrew C.
Beckmann, Jacques S.
Vollenweider, Peter
Marques-Vidal, Pedro
Whitfield, John B.
Title Genome-wide association study identifies two loci strongly affecting transferrin glycosylation
Journal name Human Molecular Genetics   Check publisher's open access policy
ISSN 0964-6906
Publication date 2011-09-01
Sub-type Article (original research)
DOI 10.1093/hmg/ddr272
Volume 20
Issue 18
Start page 3710
End page 3717
Total pages 8
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Language eng
Formatted 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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
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