Author:
Ichihara Sahoko,Yamamoto Ken,Asano Hiroyuki,Nakatochi Masahiro,Sukegawa Mayo,Ichihara Gaku,Izawa Hideo,Hirashiki Akihiro,Takatsu Fumimaro,Umeda Hisashi,Iwase Mitsunori,Inagaki Haruo,Hirayama Haruo,Sone Takahito,Nishigaki Kazuhiko,Minatoguchi Shinya,Cho Myeong-Chan,Jang Yangsoo,Kim Hyo-Soo,Park Jeong E.,Tada-Oikawa Saeko,Kitajima Hidetoshi,Matsubara Tatsuaki,Sunagawa Kenji,Shimokawa Hiroaki,Kimura Akinori,Lee Jong-Young,Murohara Toyoaki,Inoue Ituro,Yokota Mitsuhiro
Abstract
Background—
Myocardial infarction (MI) is a leading cause of death worldwide. Given that a family history is an independent risk factor for coronary artery disease, genetic variants are thought to contribute directly to the development of this condition. The identification of susceptibility genes for coronary artery disease or MI may thus help to identify high-risk individuals and offer the opportunity for disease prevention.
Methods and Results—
We designed a 5-step protocol, consisting of a genome-wide linkage study followed by association analysis, to identify novel genetic variants that confer susceptibility to coronary artery disease or MI. A genome-wide affected sib-pair linkage study with 221 Japanese families with coronary artery disease yielded a statistically significant logarithm of the odds score of 3.44 for chromosome 2p13 and MI. Further association analysis implicated Alström syndrome 1 gene (
ALMS1
) as a candidate gene within the linkage region. Validation association analysis revealed that representative single-nucleotide polymorphisms of the
ALMS1
promoter region were significantly associated with early-onset MI in both Japanese and Korean populations. Moreover, direct sequencing of the
ALMS1
coding region identified a glutamic acid repeat polymorphism in exon 1, which was subsequently found to be associated with early-onset MI.
Conclusions—
The glutamic acid repeat polymorphism of
ALMS1
identified in the present study may provide insight into the pathogenesis of early-onset MI.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Genetics (clinical),Cardiology and Cardiovascular Medicine,Genetics
Cited by
18 articles.
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