Galectin-3 is a lectin involved in fibrosis, inflammation and proliferation. Increased circulating levels of galectin-3 have been associated with various diseases, including cancer, immunological disorders, and cardiovascular disease. To enhance our knowledge on galectin-3 biology we performed the first genome-wide association study (GWAS) using the Illumina HumanCytoSNP-12 array imputed with the HapMap 2 CEU panel on plasma galectin-3 levels in 3,776 subjects and follow-up genotyping in an additional 3,516 subjects. We identified 2 genome wide significant loci associated with plasma galectin-3 levels. One locus harbours the LGALS3 gene (rs2274273; P = 2.35×10 -188) and the other locus the ABO gene (rs644234; P = 3.65×10 -47). The variance explained by the LGALS3 locus was 25.6% and by the ABO locus 3.8% and jointly they explained 29.2%. Rs2274273 lies in high linkage disequilibrium with two non-synonymous SNPs (rs4644; r 2 = 1.0, and rs4652; r 2 = 0.91) and wet lab follow-up genotyping revealed that both are strongly associated with galectin-3 levels (rs4644; P = 4.97×10 -465 and rs4652 P = 1.50×10 -421) and were also associated with LGALS3 gene-expression. The origins of our associations should be further validated by means of functional experiments. © 2012 de Boer et al.
CITATION STYLE
de Boer, R. A., Verweij, N., van Veldhuisen, D. J., Westra, H. J., Bakker, S. J. L., Gansevoort, R. T., … van der Harst, P. (2012). A Genome-Wide Association Study of Circulating Galectin-3. PLoS ONE, 7(10). https://doi.org/10.1371/journal.pone.0047385
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