title: Genetic variation in hyaluronan metabolism loci is associated with plasma plasminogen activator inhibitor-1 concentration.
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, subjects within the population-based SHARE (Study of Health Assessment and Risk in Ethnic groups) and SHARE-AP (Study of Health Assessment and Risk Evaluation in Aboriginal Peoples) 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. After imputation, more than 150,000 single nucleotide polymorphisms (SNPs) in more than 2000 loci were tested for association with plasma PAI-1 concentration. Marginal association was observed with the PAI-1 locus itself (SERPINE1; P < .05). However, 5 loci (HABP2, HSPA1A, HYAL1, MBTPS1, TARP) were associated with PAI-1 concentration at a P < 1 × 10(-5) threshold. The protein products of 2 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.
authors.affiliation: Department of Medicine, Robarts Research Institute and Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON, Canada. mlanktree2012@meds.uwo.ca
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Lanktree
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Johansen
authors.forename: Sonia S
authors.initials: SS
authors.lastname: Anand
authors.forename: A Darlene
authors.initials: AD
authors.lastname: Davis
authors.forename: Ruby
authors.initials: R
authors.lastname: Miller
authors.forename: Salim
authors.initials: S
authors.lastname: Yusuf
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hegele
mesh_terms: D044466:Asian People; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006801:Humans; D006820:Hyaluronic Acid / Q000235:genetics / Q000378:metabolism*; D006821:Hyaluronoglucosaminidase / Q000235:genetics; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D020641:Polymorphism, Single Nucleotide; D012697:Serine Endopeptidases / Q000235:genetics; D044465:White People
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D006820:Hyaluronic Acid; D006821:Hyaluronoglucosaminidase; C433550:HABP2 protein, human; D012697:Serine Endopeptidases