Genetic variation in hyaluronan metabolism loci is associated with plasma plasminogen activator inhibitor-1 concentration.
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| 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.
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| Authors | Matthew B Lanktree, Christopher T Johansen, Sonia S Anand, A Darlene Davis, Ruby Miller, Salim Yusuf, Robert A Hegele, SHARE Investigators, SHARE-AP Investigators |
| Journal | Blood (Blood) Vol. 116 Issue 12 Pg. 2160-3 (Sep 23 2010) ISSN: 1528-0020 [Electronic] United States |
| PMID | 20558613 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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