RRC ID 76369
Author Ichihara S, Yamamoto K, Asano H, Nakatochi M, Sukegawa M, Ichihara G, Izawa H, Hirashiki A, Takatsu F, Umeda H, Iwase M, Inagaki H, Hirayama H, Sone T, Nishigaki K, Minatoguchi S, Cho MC, Jang Y, Kim HS, Park JE, Tada-Oikawa S, Kitajima H, Matsubara T, Sunagawa K, Shimokawa H, Kimura A, Lee JY, Murohara T, Inoue I, Yokota M.
Title Identification of a glutamic acid repeat polymorphism of ALMS1 as a novel genetic risk marker for early-onset myocardial infarction by genome-wide linkage analysis.
Journal Circ Cardiovasc Genet
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.
Volume 6(6)
Pages 569-78
Published 2013-12-1
DOI 10.1161/CIRCGENETICS.111.000027
PMID 24122612
MeSH Age of Onset Asian People / genetics Cell Cycle Proteins Cell Line Chromosome Mapping / methods Chromosomes, Human, Pair 2 / genetics Coronary Artery Disease / ethnology Coronary Artery Disease / genetics Family Health Gene Frequency Genetic Linkage Genetic Predisposition to Disease / ethnology Genetic Predisposition to Disease / genetics* Genome-Wide Association Study / methods Genotype Glutamic Acid / genetics* Humans Japan / epidemiology Myocardial Infarction / epidemiology Myocardial Infarction / ethnology Myocardial Infarction / genetics* Odds Ratio Polymorphism, Single Nucleotide* Proteins / genetics* Repetitive Sequences, Amino Acid / genetics* Republic of Korea / epidemiology Risk Factors
Human and Animal Cells Epstein-Barr virus–transformed B-cell lines derived from 92 healthy Japanese subjects