Document Detail

Functional SNPs in the lymphotoxin-alpha gene that are associated with susceptibility to myocardial infarction.
MedLine Citation:
PMID:  12426569     Owner:  NLM     Status:  MEDLINE    
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.
Kouichi Ozaki; Yozo Ohnishi; Aritoshi Iida; Akihiko Sekine; Ryo Yamada; Tatsuhiko Tsunoda; Hiroshi Sato; Hideyuki Sato; Masatsugu Hori; Yusuke Nakamura; Toshihiro Tanaka
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2002-11-11
Journal Detail:
Title:  Nature genetics     Volume:  32     ISSN:  1061-4036     ISO Abbreviation:  Nat. Genet.     Publication Date:  2002 Dec 
Date Detail:
Created Date:  2002-11-28     Completed Date:  2003-01-17     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9216904     Medline TA:  Nat Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  650-4     Citation Subset:  IM    
Laboratory for Cardiovascular Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
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MeSH Terms
Amino Acid Substitution
Case-Control Studies
Cells, Cultured
Chromosome Mapping
Chromosomes, Human, Pair 6
Coronary Vessels / metabolism
Databases, Genetic
Gene Frequency
Genetic Predisposition to Disease*
Genetic Testing
Jurkat Cells
Linkage Disequilibrium
Lymphotoxin-alpha / genetics*
Middle Aged
Muscle, Smooth, Vascular / cytology,  physiology
Myocardial Infarction / genetics*
Polymorphism, Single Nucleotide*
Recombinant Fusion Proteins / metabolism
Sequence Analysis, DNA
Transcription, Genetic
Vascular Cell Adhesion Molecule-1 / biosynthesis
Reg. No./Substance:
0/Lymphotoxin-alpha; 0/Recombinant Fusion Proteins; 0/Vascular Cell Adhesion Molecule-1
Erratum In:
Nat Genet. 2003 Jan;33(1):107.

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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