Publication: Genetic variation in hyaluronan metabolism loci is associated with plasma plasminogen activator inhibitor-1 concentration.

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Title	Genetic variation in hyaluronan metabolism loci is associated with plasma plasminogen activator inhibitor-1 concentration.
Authors/Editors*	Lanktree MB, Johansen CT, Anand SS, Yusuf S, Hegele RA
Where published*	Blood
How published*	Journal
Year*	2010
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Link	20558613
Abstract	Elevated plasma plasminogen activator inhibitor-1 (PAI-1) concentration is associated with cardiovascular disease risk. PAI-1 is the primary inhibitor of fibrinolysis within both the circulation and the arterial wall, playing roles in both atherosclerosis and thrombosis. To define the heritable component, the population-based SHARE and SHARE-AP studies, composed of Canadians of South Asian (n=298), Chinese (n=284), European (n=227), and Aboriginal (n=284) descent were genotyped using the gene-centric Illumina HumanCVD BeadChip. Following imputation, >150 000 SNPs in >2000 loci were tested for association with plasma PAI-1 concentration. Marginal association was observed with the PAI-1 locus itself (SERPINE1; P < 0.05). However, five loci (HABP2, HSPA1A, HYAL1, MBTPS1, TARP) were associated with PAI-1 concentration at a P < 1 x 10(-5) threshold. The protein products of two of these loci, hyaluronan binding protein 2 (HABP2) and hyaluronoglucosaminidase 1 (HYAL1), play key roles in hyaluronan metabolism, providing genetic evidence to link these pathways.