Abstract P110: Gene-Gene Interaction: SERPINE1 Interacts with ANRIL in Association with Coronary Artery Disease and Coronary Artery Calcium in a Non-Hispanic Population
Introduction: Long non-coding RNAs (lncRNA) are important regulators of gene expression. ANRIL (CDKN2B-AS1) is an anti-sense lncRNA coded for at the Chr9p21 locus. GWAS have reported SNPs in the Chr9p21 to be associated with clinical coronary artery disease (CAD) and coronary artery calcium (CAC). A knockdown study of two isoforms of ANRIL reported the potential of ANRIL’s regulation of SERPINE1 expression. SERPINE1 encodes plasminogen activator inhibitor-1 (PAI-1) and has been reported to be associated with CAD and CAC. The 3’UTR of SERPINE1 has been reported to bind miRNA and lncRNA suggesting ANRIL may modify SERPINE1’s association with CAD and CAC.
Hypothesis: We hypothesized that rs7242 or rs1050955, covering the LD of the 3’ UTR of SERPINE1, will interact with SNPs within ANRIL to affect their association with self-reported CAD and CAC in non-Hispanic Whites (NHW, n=6103) and African Americans (AA, n=2549) in the COPDGene Study.
Methods: Interaction of SNPs from Illumina HumanOmniExpress Beadchip for ANRIL, and rs7242 and rs1050955 were evaluated in an additive genetic model with a cross-product interaction term. Logistic regression was used to evaluate the association of CAD (Yes/No) and CAC (Yes/No) with the SNP-SNP interactions, while controlling for genetic ancestry, ascertainment, age, sex, BMI, diabetes, hypertension, high cholesterol and pack-years of smoking. Analyses were stratified by race.
Results: A significant interaction between rs7242 (SERPINE1) and rs7049105 (ANRIL) and CAD (p=0.0004) and CAC (p=0.0023) were found in NHW (Figure 1). The risk estimates for the rs7242 G allele in SERPINE1 were higher in those with the rs7049105 AA genotype in ANRIL but were lower in those with the rs7049105 GG genotype in ANRIL. We did not find any significant interactions in AA.
Conclusion: In this study, the previously identified GWAS signal for CAD and CAC in Chr9p21 (ANRIL) interacts with a SNP in SERPINE1. This may be due to ANRIL lncRNA influences on gene expression of SERPINE1 and increases the risk of both CAC and CAD.
Author Disclosures: K.A. Pratte: None. S.M. Lutz: None. T.E. Fingerlin: None. R.P. Bowler: None. G.L. Kinney: None. K.A. Young: None. M.H. Cho: None. R. Casaburi: None. E.K. Silverman: None. J.D. Crapo: None. M.J. Budoff: None. J.E. Hokanson: None.
- © 2017 by American Heart Association, Inc.