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Peakwide mapping on chromosome 3q13 identifies the kalirin gene as a novel candidate gene for coronary artery disease.

Publication ,  Journal Article
Wang, L; Hauser, ER; Shah, SH; Pericak-Vance, MA; Haynes, C; Crosslin, D; Harris, M; Nelson, S; Hale, AB; Granger, CB; Haines, JL; Jones, CJH ...
Published in: Am J Hum Genet
April 2007

A susceptibility locus for coronary artery disease (CAD) has been mapped to chromosome 3q13-21 in a linkage study of early-onset CAD. We completed an association-mapping study across the 1-LOD-unit-down supporting interval, using two independent white case-control data sets (CATHGEN, initial and validation) to evaluate association under the peak. Single-nucleotide polymorphisms (SNPs) evenly spaced at 100-kb intervals were screened in the initial data set (N=468). Promising SNPs (P<.1) were then examined in the validation data set (N=514). Significant findings (P<.05) in the combined initial and validation data sets were further evaluated in multiple independent data sets, including a family-based data set (N=2,954), an African American case-control data set (N=190), and an additional white control data set (N=255). The association between genotype and aortic atherosclerosis was examined in 145 human aortas. The peakwide survey found evidence of association in SNPs from multiple genes. The strongest associations were found in three SNPs from the kalirin (KALRN) gene, especially in patients with early-onset CAD (P=.00001-00028 in the combined CATHGEN data sets). In-depth investigation of the gene found that an intronic SNP, rs9289231, was associated with early-onset CAD in all white data sets examined (P<.05). In the joint analysis of all white early-onset CAD cases (N=332) and controls (N=546), rs9289231 was highly significant (P=.00008), with an odds-ratio estimate of 2.1. Furthermore, the risk allele of this SNP was associated with atherosclerosis burden (P=.03) in 145 human aortas. KALRN is a protein with many functions, including the inhibition of inducible nitric oxide synthase and guanine-exchange-factor activity. KALRN and two other associated genes identified in this study (CDGAP and MYLK) belong to the Rho GTPase-signaling pathway. Our data suggest the importance of the KALRN gene and the Rho GTPase-signaling pathway in the pathogenesis of CAD.

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Published In

Am J Hum Genet

DOI

ISSN

0002-9297

Publication Date

April 2007

Volume

80

Issue

4

Start / End Page

650 / 663

Location

United States

Related Subject Headings

  • White People
  • United States
  • Signal Transduction
  • Protein Serine-Threonine Kinases
  • Polymorphism, Single Nucleotide
  • Odds Ratio
  • Middle Aged
  • Male
  • Logistic Models
  • Humans
 

Citation

APA
Chicago
ICMJE
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Wang, L., Hauser, E. R., Shah, S. H., Pericak-Vance, M. A., Haynes, C., Crosslin, D., … Vance, J. M. (2007). Peakwide mapping on chromosome 3q13 identifies the kalirin gene as a novel candidate gene for coronary artery disease. Am J Hum Genet, 80(4), 650–663. https://doi.org/10.1086/512981
Wang, Liyong, Elizabeth R. Hauser, Svati H. Shah, Margaret A. Pericak-Vance, Carol Haynes, David Crosslin, Marco Harris, et al. “Peakwide mapping on chromosome 3q13 identifies the kalirin gene as a novel candidate gene for coronary artery disease.Am J Hum Genet 80, no. 4 (April 2007): 650–63. https://doi.org/10.1086/512981.
Wang L, Hauser ER, Shah SH, Pericak-Vance MA, Haynes C, Crosslin D, et al. Peakwide mapping on chromosome 3q13 identifies the kalirin gene as a novel candidate gene for coronary artery disease. Am J Hum Genet. 2007 Apr;80(4):650–63.
Wang, Liyong, et al. “Peakwide mapping on chromosome 3q13 identifies the kalirin gene as a novel candidate gene for coronary artery disease.Am J Hum Genet, vol. 80, no. 4, Apr. 2007, pp. 650–63. Pubmed, doi:10.1086/512981.
Wang L, Hauser ER, Shah SH, Pericak-Vance MA, Haynes C, Crosslin D, Harris M, Nelson S, Hale AB, Granger CB, Haines JL, Jones CJH, Crossman D, Seo D, Gregory SG, Kraus WE, Goldschmidt-Clermont PJ, Vance JM. Peakwide mapping on chromosome 3q13 identifies the kalirin gene as a novel candidate gene for coronary artery disease. Am J Hum Genet. 2007 Apr;80(4):650–663.
Journal cover image

Published In

Am J Hum Genet

DOI

ISSN

0002-9297

Publication Date

April 2007

Volume

80

Issue

4

Start / End Page

650 / 663

Location

United States

Related Subject Headings

  • White People
  • United States
  • Signal Transduction
  • Protein Serine-Threonine Kinases
  • Polymorphism, Single Nucleotide
  • Odds Ratio
  • Middle Aged
  • Male
  • Logistic Models
  • Humans