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Functional SNPs in the lymphotoxin-alpha gene that are associated with susceptibility to myocardial infarction.

Authors: Ozaki, K  Ohnishi, Y  Iida, A  Sekine, A  Yamada, R  Tsunoda, T  Sato, H 
Citation: Ozaki K, etal., Nat Genet. 2002 Dec;32(4):650-4. Epub 2002 Nov 11.
Pubmed: (View Article at PubMed) PMID:12426569

By means of a large-scale, case-control association study using 92,788 gene-based single-nucleotide polymorphism (SNP) markers, we identified a candidate locus on chromosome 6p21 associated with susceptibility to myocardial infarction. Subsequent linkage-disequilibrium (LD) mapping and analyses of haplotype structure showed significant associations between myocardial infarction and a single 50 kb halpotype comprised of five SNPs in LTA (encoding lymphotoxin-alpha), NFKBIL1 (encoding nuclear factor of kappa light polypeptide gene enhancer in B cells, inhibitor-like 1) and BAT1 (encoding HLA-B associated transcript 1). Homozygosity with respect to each of the two SNPs in LTA was significantly associated with increased risk for myocardial infarction (odds ratio = 1.78, chi(2) = 21.6, P = 0.00000033; 1,133 affected individuals versus 1,006 controls). In vitro functional analyses indicated that one SNP in the coding region of LTA, which changed an amino-acid residue from threonine to asparagine (Thr26Asn), effected a twofold increase in induction of several cell-adhesion molecules, including VCAM1, in vascular smooth-muscle cells of human coronary artery. Moreover, the SNP, in intron 1 of LTA, enhanced the transcriptional level of LTA. These results indicate that variants in the LTA are risk factors for myocardial infraction and implicate LTA in the pathogenesis of the disorder.

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RGD Object Information
RGD ID: 1580417
Created: 2006-07-27
Species: All species
Last Modified: 2006-07-27
Status: ACTIVE



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