| First Author | Wang L | Year | 2008 |
| Journal | Ann Hum Genet | Volume | 72 |
| Issue | Pt 4 | Pages | 443-53 |
| PubMed ID | 18318786 | Mgi Jnum | J:134451 |
| Mgi Id | MGI:3785860 | Doi | 10.1111/j.1469-1809.2008.00433.x |
| Citation | Wang L, et al. (2008) Polymorphisms of the tumor suppressor gene LSAMP are associated with left main coronary artery disease. Ann Hum Genet 72(Pt 4):443-53 |
| abstractText | Previous association mapping on chromosome 3q13-21 detected evidence for association at the limbic system-associated membrane protein (LSAMP) gene in individuals with late-onset coronary artery disease (CAD). LSAMP has never been implicated in the pathogenesis of CAD. We sought to thoroughly characterize the association and the gene. Non-redundant single nucleotide polymorphisms (SNPs) across the gene were examined in an initial dataset (168 cases with late-onset CAD, 149 controls). Stratification analysis on left main CAD (N = 102) revealed stronger association, which was further validated in a validation dataset (141 cases with left main CAD, 215 controls), a third control dataset (N = 255), and a family-based dataset (N = 2954). A haplotype residing in a novel alternative transcript of the LSAMP gene was significant in all independent case-control datasets (p = 0.0001 to 0.0205) and highly significant in the joint analysis (p = 0.00004). Lower expression of the novel alternative transcript was associated with the risk haplotype (p = 0.0002) and atherosclerosis burden in human aortas (p = 0.0001). Furthermore, silencing LSAMP expression in human aortic smooth muscle cells (SMCs) substantially augmented SMC proliferation (p<0.01). Therefore, the risk conferred by the LSAMP haplotype appears to be mediated by LSAMP down-regulation, which may promote SMC proliferation in the arterial wall and progression of atherosclerosis. |
