RRC ID 42796
Author 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.
Title Identification of a novel non-coding RNA, MIAT, that confers risk of myocardial infarction.
Journal 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.
Volume 51(12)
Pages 1087-1099
Published 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
Times Cited 363
WOS Category GENETICS & HEREDITY
Resource
Human and Animal Cells 293(RCB1637)