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Polymorphisms of the tumor suppressor gene LSAMP are associated with left main coronary artery disease.

Publication ,  Journal Article
Wang, L; Hauser, ER; Shah, SH; Seo, D; Sivashanmugam, P; Exum, ST; Gregory, SG; Granger, CB; Haines, JL; Jones, CJH; Crossman, D; Haynes, C ...
Published in: Ann Hum Genet
July 2008

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.

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Published In

Ann Hum Genet

DOI

ISSN

0003-4800

Publication Date

July 2008

Volume

72

Issue

Pt 4

Start / End Page

443 / 453

Location

England

Related Subject Headings

  • Tumor Suppressor Proteins
  • Risk Factors
  • Promoter Regions, Genetic
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Male
  • Humans
  • Haplotypes
  • Genetics & Heredity
  • Gene Expression
 

Citation

APA
Chicago
ICMJE
MLA
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Wang, L., Hauser, E. R., Shah, S. H., Seo, D., Sivashanmugam, P., Exum, S. T., … Vance, J. M. (2008). Polymorphisms of the tumor suppressor gene LSAMP are associated with left main coronary artery disease. Ann Hum Genet, 72(Pt 4), 443–453. https://doi.org/10.1111/j.1469-1809.2008.00433.x
Wang, L., E. R. Hauser, S. H. Shah, D. Seo, P. Sivashanmugam, S. T. Exum, S. G. Gregory, et al. “Polymorphisms of the tumor suppressor gene LSAMP are associated with left main coronary artery disease.Ann Hum Genet 72, no. Pt 4 (July 2008): 443–53. https://doi.org/10.1111/j.1469-1809.2008.00433.x.
Wang L, Hauser ER, Shah SH, Seo D, Sivashanmugam P, Exum ST, et al. Polymorphisms of the tumor suppressor gene LSAMP are associated with left main coronary artery disease. Ann Hum Genet. 2008 Jul;72(Pt 4):443–53.
Wang, L., et al. “Polymorphisms of the tumor suppressor gene LSAMP are associated with left main coronary artery disease.Ann Hum Genet, vol. 72, no. Pt 4, July 2008, pp. 443–53. Pubmed, doi:10.1111/j.1469-1809.2008.00433.x.
Wang L, Hauser ER, Shah SH, Seo D, Sivashanmugam P, Exum ST, Gregory SG, Granger CB, Haines JL, Jones CJH, Crossman D, Haynes C, Kraus WE, Freedman NJ, Pericak-Vance MA, Goldschmidt-Clermont PJ, Vance JM. Polymorphisms of the tumor suppressor gene LSAMP are associated with left main coronary artery disease. Ann Hum Genet. 2008 Jul;72(Pt 4):443–453.
Journal cover image

Published In

Ann Hum Genet

DOI

ISSN

0003-4800

Publication Date

July 2008

Volume

72

Issue

Pt 4

Start / End Page

443 / 453

Location

England

Related Subject Headings

  • Tumor Suppressor Proteins
  • Risk Factors
  • Promoter Regions, Genetic
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Male
  • Humans
  • Haplotypes
  • Genetics & Heredity
  • Gene Expression