| RRC ID |
42796
|
| 著者 |
Ishii N, Ozaki K, Sato H, Mizuno H, Susumu Saito, Takahashi A, Miyamoto Y, Ikegawa S, Kamatani N, Hori M, Satoshi Saito, Nakamura Y, Tanaka T.
|
| タイトル |
Identification of a novel non-coding RNA, MIAT, that confers risk of myocardial infarction.
|
| ジャーナル |
J Hum Genet
|
| Abstract |
Through a large-scale case-control association study using 52,608 haplotype-based single nucleotide polymorphism (SNP) markers, we identified a susceptible locus for myocardial infarction (MI) on chromosome 22q12.1. Following linkage disequilibrium (LD) mapping, haplotype analyses revealed that six SNPs in this locus, all of which were in complete LD, showed markedly significant association with MI (chi2=25.27, P=0.0000005; comparison of allele frequency, 3,435 affected individuals versus 3,774 controls, in the case of intron 1 5,338 C>T; rs2331291). Within this locus, we isolated a complete cDNA of a novel gene, designated myocardial infarction associated transcript (MIAT). MIAT has five exons, and in vitro translation assay showed that MIAT did not encode any translational product, indicating that this is likely to be a functional RNA. In vitro functional analyses revealed that the minor variant of one SNP in exon 5 increased transcriptional level of the novel gene. Moreover, unidentified nuclear protein(s) bound more intensely to risk allele than non-risk allele. These results indicate that the altered expression of MIAT by the SNP may play some role in the pathogenesis of MI.
|
| 巻・号 |
51(12)
|
| ページ |
1087-1099
|
| 公開日 |
2006-1-1
|
| DOI |
10.1007/s10038-006-0070-9
|
| PII |
10.1007/s10038-006-0070-9
|
| PMID |
17066261
|
| MeSH |
Alleles
Case-Control Studies
Chromosomes, Human, Pair 22
Electrophoretic Mobility Shift Assay
Genetic Markers
Genetic Predisposition to Disease*
Genetic Variation
Haplotypes
Humans
Linkage Disequilibrium
Models, Genetic
Myocardial Infarction / diagnosis
Myocardial Infarction / genetics*
Polymorphism, Single Nucleotide*
RNA Stability / genetics
RNA, Long Noncoding
RNA, Untranslated / genetics*
Risk Factors
Transcription, Genetic
|
| IF |
2.831
|
| 引用数 |
363
|
|
WOS 分野
|
GENETICS & HEREDITY
|
| リソース情報 |
| ヒト・動物細胞 |
293(RCB1637) |
