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.
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.
  
  
  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.
authors.forename: Sahoko
authors.initials: S
authors.lastname: Ichihara
authors.forename: Ken
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Hiroyuki
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authors.lastname: Asano
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nakatochi
authors.forename: Mayo
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authors.lastname: Sukegawa
authors.forename: Gaku
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authors.lastname: Ichihara
authors.forename: Hideo
authors.initials: H
authors.lastname: Izawa
authors.forename: Akihiro
authors.initials: A
authors.lastname: Hirashiki
authors.forename: Fumimaro
authors.initials: F
authors.lastname: Takatsu
authors.forename: Hisashi
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authors.lastname: Umeda
authors.forename: Mitsunori
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authors.lastname: Iwase
authors.forename: Haruo
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authors.lastname: Inagaki
authors.forename: Haruo
authors.initials: H
authors.lastname: Hirayama
authors.forename: Takahito
authors.initials: T
authors.lastname: Sone
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nishigaki
authors.forename: Shinya
authors.initials: S
authors.lastname: Minatoguchi
authors.forename: Myeong-Chan
authors.initials: MC
authors.lastname: Cho
authors.forename: Yangsoo
authors.initials: Y
authors.lastname: Jang
authors.forename: Hyo-Soo
authors.initials: HS
authors.lastname: Kim
authors.forename: Jeong E
authors.initials: JE
authors.lastname: Park
authors.forename: Saeko
authors.initials: S
authors.lastname: Tada-Oikawa
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Kitajima
authors.forename: Tatsuaki
authors.initials: T
authors.lastname: Matsubara
authors.forename: Kenji
authors.initials: K
authors.lastname: Sunagawa
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shimokawa
authors.forename: Akinori
authors.initials: A
authors.lastname: Kimura
authors.forename: Jong-Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Murohara
authors.forename: Ituro
authors.initials: I
authors.lastname: Inoue
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yokota
mesh_terms: D017668:Age of Onset; D044466:Asian People / Q000235:genetics; D018797:Cell Cycle Proteins; D002460:Cell Line; D002874:Chromosome Mapping / Q000379:methods; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D003324:Coronary Artery Disease / Q000208:ethnology / Q000235:genetics; D005192:Family Health; D005787:Gene Frequency; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D018698:Glutamic Acid / Q000235:genetics*; D006801:Humans; D007564:Japan / Q000453:epidemiology; D009203:Myocardial Infarction / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D020449:Repetitive Sequences, Amino Acid / Q000235:genetics*; D056910:Republic of Korea / Q000453:epidemiology; D012307:Risk Factors
chemical_list: C490729:ALMS1 protein, human; D018797:Cell Cycle Proteins; D011506:Proteins; D018698:Glutamic Acid
keywords: genetic association studies; genetics; genome-wide association study; linkage mapping; myocardial infarction; susceptibility, genetic