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Functional SNPs in the lymphotoxin-α gene that are associated with susceptibility to myocardial infarction.
- Source :
-
Nature Genetics . Dec2002, Vol. 32 Issue 4, p650. 5p. - Publication Year :
- 2002
-
Abstract
- 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-α), NFKBIL1 (encoding nuclear factor of κ 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, χ2 = 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *GENETIC polymorphisms
*TUMOR necrosis factors
*MYOCARDIAL infarction
Subjects
Details
- Language :
- English
- ISSN :
- 10614036
- Volume :
- 32
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- Nature Genetics
- Publication Type :
- Academic Journal
- Accession number :
- 8584049
- Full Text :
- https://doi.org/10.1038/ng1047