Abstract P361: The First Genome-Wide Association Study (GWAS) of GlycA, an NMR-Derived Marker of Inflammation, Reveals Associations With a Variant in the Intron of TXNL4B Across Two Cohorts
Markers of inflammation reflect metabolic dysfunction and may predict incident cardiovascular events. GlycA is a new NMR-derived plasma marker of inflammation. Our goal was to undertake first characterization of the genetic variants associated with fasting GlycA, to elucidate the pathways from genes to inflammation. We completed a GWAS in the Caucasian-ancestry population of The Multi-Ethnic Study of Atherosclerosis (MESA; N=2,520; 48% male, mean age 62.7 y). We specified linear regressions models with GlycA as the outcome, and ~2.5 million single nucleotide polymorphisms (SNPs) directly genotyped or imputed from HapMap as the predictors in separate models; all models additionally controlled for age, gender, alcohol intake (g/day), smoking status (yes / no) and 4 principal components of population structure. In MESA, 5 SNPs reached genome-wide levels of significance (P<10-8; Table 1). Forty six SNPs reached a ‘discovery threshold’ of P<10-5 in MESA, but only one (rs217181; minor allele frequency = .18) replicated in the Genetics of Lipid Lowering Drug Network (GOLDN; N=817; 48% male, mean age=48.8 years) after an FDR multiple testing correction. Rs217181 is located in the intron of TXNL4B, thioredoxin-like 4B, and in close proximity to HP, Haptoglobin, and HPR, Haptoglobin-related Protein. Rs217181 has been validated as associating with levels of haptoglobin protein. Haptoglobin is released by the liver and reduces hemoglobin’s oxidative activity. Our data suggests that rs217181 is involved in inflammation status, and may be a risk factor for adverse cardiovascular events. We would encourage replication of these findings in other cohorts, and are undertaking examination of this association in non-Caucasian individuals.
Author Disclosures: A.C. Frazier-Wood: B. Research Grant; Significant; American Heart Association, USDA. S. Aslibekyan: None. I.B. Borecki: None. J.M. Ordovas: None. J.I. Rotter: None. M.Y. Tsai: None. D.K. Arnett: None. S.S. Rich: None.
This research has received full or partial funding support from the American Heart Association, South Central Affiliate (Arkansas, New Mexico, Oklahoma & Texas).
- © 2015 by American Heart Association, Inc.