W. Hernandez,1 E. R. Gamazon,1 A. Konkashbaev,1 A. Konkashbaev,1 R. A. Kittles,2 L. H. Cavallari,3 M. A. Perera1; 1The University of Chicago, Chicago, IL, 2University of Arizona College of Medicine, Tucson, AZ, 3University of Florida, Gainesville, FL
BACKGROUND: Venous thromboembolism (VTE) is a chronic multifactorial disease and the third most common life-threatening cardiovascular condition resulting in high rates of hospitalization and mortality. African Americans (AAs) have the highest VTE incidence and mortality rates. Although studies suggest that VTE is highly heritable, few associations between VTE risk and genetic variants have been established, especially for AAs. In this study, we present preliminary findings from the first genome-wide association study (GWAS) and risk of VTE conducted exclusively on 574 AAs.
METHODS: We genotyped 137 VTE patients (cases) on stable warfarin dose and 437 controls using Ilumina 610 Quad BeadChip.
RESULTS: Our preliminary findings revealed variants in PTGER3 (rs570021), PPP1R12B (rs705744), SLC22A3 (rs9364552), SLC39A11 (rs951284), and MGST1 (rs2975139) were associated with increased risk of VTE (ORs= 2.2 - 2.6; P< 5.0x10-8 and rs10234060 and rs711831 were found to decrease risk of VTE (OR=0.40 and 0.44, respectively; P< 5.0x10-8). Furthermore, bioinformatics analysis using whole blood expression quantitative trait loci (eQTLs) from AAs identified rs9364552 to be a cis-eQTL (β=-0.19; P=0.02) for plasminogen (PLG) which is crucial in breaking down fibrin in blood clots. Individuals carrying the rs9364552 minor allele would express lower levels of PLG, increasing their risk of VTE. SLC22A3 and PLG have been shown to affect lipoprotein(a) levels - an independent risk factor for VTE. Currently, we are in the process of validating these findings in an independent AA cohort of VTE.
CONCLUSION: Our study provides new molecular insight into the underlying mechanism regulating VTE susceptibility in AAs and has identified a new potential clinical variable contributing to hypercoagulable states.