A Genome-Wide Association Study of Circulating Galectin-3

• Published in: PloS one Vol. 7; no. 10; p. e47385
• Main Authors: de Boer, Rudolf A., Verweij, Niek, van Veldhuisen, Dirk J., Westra, Harm-Jan, Bakker, Stephan J. L., Gansevoort, Ron T., Muller Kobold, Anneke C., van Gilst, Wiek H., Franke, Lude, Leach, Irene Mateo, van der Harst, Pim
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 09.10.2012; Public Library of Science (PLoS)
• Subjects: ABO system; Biology; Cancer; Cardiology; Cardiovascular diseases; Cell adhesion & migration; Female; Fibrosis; Galectin 3 - blood; Galectin 3 - genetics; Galectin-3; Gene expression; Genes; Genetic aspects; Genetics; Genome-wide association studies; Genome-Wide Association Study - methods; Genomes; Genomics; Genotype; Genotyping; Heart failure; Humans; Immunology; Inflammation; Internal medicine; Lectins; LGALS3 gene; Linkage disequilibrium; Loci; Male; Medicine; Polymorphism, Single Nucleotide - genetics; Population; Single-nucleotide polymorphism; Netherlands
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0047385

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.