Abstract 18169: Genetic Association Study of Circulating Galectin-3 in the General Community Identifies a Variant Associated With Myocardial Infarction
Introduction: Galectin (Gal)-3 deficiency has been associated with accelerated atherosclerosis and proinflammatory pathways in mice but its implication in human atherosclerosis is unknown. The variability in Gal-3 levels may be inherited. We sought to determine the genetic variants associated with circulating Gal-3 levels and its impact on vascular events in the general community.
Methods: Serum Gal-3 levels were measured in a random sample of 1,838 Olmsted County, MN residents aged ≥ 45 years. Mean follow up time was 11.1 years. Genotyping was performed by using the Cardio-MetaboChip in 920 random individuals who served as the discovery cohort and replicated in a separate population of 918 subjects. An additive genotype model based on number of copies of the minor allele was used for analyses.
Results: There were 4 genome-wide significant (p≤3.9 X 10-7) single nucleotide polymorphisms (SNPs) in chromosome 14 in GCH1 and FBXO034 genes (rs943912, rs8022453, rs10131232, rs7148669) that were associated with Gal-3 levels in the discovery cohort (Figure). Three of these SNPs, all in GCH1, were replicated after correction for multiple testing. The most significant SNP, rs10131232, was intronic in GCH1 gene with a minor allele frequency=0.342 and was associated with lower Gal-3 levels (β=-0.095, p=1.35X10-17 in the discovery cohort, and β=-0.086, p=4.41X10-17 in the replication cohort). The minor allele of rs10131232 was associated with an increased risk for myocardial infarction (MI) (HR=1.3, p=0.03) as compared to the major allele. Association with MI was maintained after controlling for age, sex, body mass index, diabetes mellitus, hypertension, smoking, and total cholesterol (HR=1.2, p=0.04).
Conclusions: A genetic association study of circulating Gal-3 resulted in the identification and replication of 3 SNPs in the GCH1 gene. The most significant SNP rs10131232 was associated with lower Gal-3 levels and an increased risk for MI in the general community.
Author Disclosures: N. Pereira: None. C. Scott: None. G. Jenkins: None. D. Robinson: None. N. Tosakulwong: None. J. Burnett: None. R. Weinshilboum: None. M. Redfield: Honoraria; Modest; HFSA CME presentation. Consultant/Advisory Board; Modest; Eli Lily Co., Novartis- unpaid advisory.
- © 2014 by American Heart Association, Inc.