論文 - 詳細
| RRC ID | 41722 |
|---|---|
| 著者 | Ozaki K, Ohnishi Y, Iida A, Sekine A, Yamada R, Tsunoda T, Sato H, Sato H, Hori M, Nakamura Y, Tanaka T. |
| タイトル | Functional SNPs in the lymphotoxin-alpha gene that are associated with susceptibility to myocardial infarction. |
| ジャーナル | Nat Genet |
| 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-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. |
| 巻・号 | 32(4) |
| ページ | 650-4 |
| 公開日 | 2002-12-1 |
| DOI | 10.1038/ng1047 |
| PII | ng1047 |
| PMID | 12426569 |
| MeSH | Aged 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 Genotype Haplotypes Homozygote Humans Introns Jurkat Cells Linkage Disequilibrium Lymphotoxin-alpha / genetics* Middle Aged Muscle, Smooth, Vascular / cytology Muscle, Smooth, Vascular / physiology Myocardial Infarction / genetics* Polymorphism, Single Nucleotide* Recombinant Fusion Proteins / metabolism Sequence Analysis, DNA Transcription, Genetic Vascular Cell Adhesion Molecule-1 / biosynthesis |
| IF | 27.605 |
| 引用数 | 613 |
| WOS 分野 | GENETICS & HEREDITY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 55 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | Jurkat(RCB0806) |