| Literature DB >> 26791355 |
Atsuko Konta1,2, Kouichi Ozaki1, Yasuhiko Sakata3,4, Atsushi Takahashi5, Takashi Morizono6, Shinichiro Suna3, Yoshihiro Onouchi1, Tatsuhiko Tsunoda6,7, Michiaki Kubo8, Issei Komuro3,9, Yoshinobu Eishi2, Toshihiro Tanaka1,10,11.
Abstract
Coronary artery disease (CAD) including myocardial infarction is one of the leading causes of death in many countries. Similar to other common diseases, its pathogenesis is thought to result from complex interactions among multiple genetic and environmental factors. Recent large-scale genetic association analysis for CAD identified 15 new loci. We examined the reproducibility of these previous association findings with 7990 cases and 6582 controls in a Japanese population. We found a convincing association of rs9319428 in FLT1, encoding fms-related tyrosine kinase 1 (P=5.98 × 10(-8)). Fine mapping using tag single-nucleotide polymorphisms (SNPs) at FLT1 locus revealed that another SNP (rs74412485) showed more profound genetic effect for CAD (P=2.85 × 10(-12)). The SNP, located in intron 1 in FLT1, enhanced the transcriptional level of FLT1. RNA interference experiment against FLT1 showed that the suppression of FLT1 resulted in decreased expression of inflammatory adhesion molecules. Expression of FLT1 was observed in endothelial cells of human coronary artery. Our results indicate that the genetically coded increased expression of FLT1 by a functional SNP implicates activation in an inflammatory cascade that might eventually lead to CAD.Entities:
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Year: 2016 PMID： 26791355 DOI： 10.1038/jhg.2015.171
Source DB: PubMed Journal: J Hum Genet ISSN： 1434-5161 Impact factor: 3.172