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

Sahoko Ichihara, Ken Yamamoto, Hiroyuki Asano, Masahiro Nakatochi, Mayo Sukegawa, Gaku Ichihara, Hideo Izawa, Akihiro Hirashiki, Fumimaro Takatsu, Hisashi Umeda, Mitsunori Iwase, Haruo Inagaki, Haruo Hirayama, Takahito Sone, Kazuhiko Nishigaki, Shinya Minatoguchi, Myeong Chan Cho, Yangsoo Jang, Hyo Soo Kim, Jeong E. ParkSaeko Tada-Oikawa, Hidetoshi Kitajima, Tatsuaki Matsubara, Kenji Sunagawa, Hiroaki Shimokawa, Akinori Kimura, Jong Young Lee, Toyoaki Murohara, Ituro Inoue, Mitsuhiro Yokota

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)569-578
Number of pages10
JournalCirculation: Cardiovascular Genetics
Volume6
Issue number6
DOIs
Publication statusPublished - 01-12-2013

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Genetic Markers
Glutamic Acid
Myocardial Infarction
Genome
Coronary Artery Disease
Genes
Genetic Promoter Regions
Single Nucleotide Polymorphism
Cause of Death
Exons
Chromosomes
Population

All Science Journal Classification (ASJC) codes

  • Genetics
  • Cardiology and Cardiovascular Medicine
  • Genetics(clinical)

Cite this

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. / 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. In: Circulation: Cardiovascular Genetics. 2013 ; Vol. 6, No. 6. pp. 569-578.
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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. 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 Alstr{\"o}m 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.",
author = "Sahoko Ichihara and Ken Yamamoto and Hiroyuki Asano and Masahiro Nakatochi and Mayo Sukegawa and Gaku Ichihara and Hideo Izawa and Akihiro Hirashiki and Fumimaro Takatsu and Hisashi Umeda and Mitsunori Iwase and Haruo Inagaki and Haruo Hirayama and Takahito Sone and Kazuhiko Nishigaki and Shinya Minatoguchi and Cho, {Myeong Chan} and Yangsoo Jang and Kim, {Hyo Soo} and Park, {Jeong E.} and Saeko Tada-Oikawa and Hidetoshi Kitajima and Tatsuaki Matsubara and Kenji Sunagawa and Hiroaki Shimokawa and Akinori Kimura and Lee, {Jong Young} and Toyoaki Murohara and Ituro Inoue and Mitsuhiro Yokota",
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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 2013, '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', Circulation: Cardiovascular Genetics, vol. 6, no. 6, pp. 569-578. https://doi.org/10.1161/CIRCGENETICS.111.000027

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. / 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.

In: Circulation: Cardiovascular Genetics, Vol. 6, No. 6, 01.12.2013, p. 569-578.

Research output: Contribution to journalArticle

TY - JOUR

T1 - 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

AU - Ichihara, Sahoko

AU - Yamamoto, Ken

AU - Asano, Hiroyuki

AU - Nakatochi, Masahiro

AU - Sukegawa, Mayo

AU - Ichihara, Gaku

AU - Izawa, Hideo

AU - Hirashiki, Akihiro

AU - Takatsu, Fumimaro

AU - Umeda, Hisashi

AU - Iwase, Mitsunori

AU - Inagaki, Haruo

AU - Hirayama, Haruo

AU - Sone, Takahito

AU - Nishigaki, Kazuhiko

AU - Minatoguchi, Shinya

AU - Cho, Myeong Chan

AU - Jang, Yangsoo

AU - Kim, Hyo Soo

AU - Park, Jeong E.

AU - Tada-Oikawa, Saeko

AU - Kitajima, Hidetoshi

AU - Matsubara, Tatsuaki

AU - Sunagawa, Kenji

AU - Shimokawa, Hiroaki

AU - Kimura, Akinori

AU - Lee, Jong Young

AU - Murohara, Toyoaki

AU - Inoue, Ituro

AU - Yokota, Mitsuhiro

PY - 2013/12/1

Y1 - 2013/12/1

N2 - 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.

AB - 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.

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U2 - 10.1161/CIRCGENETICS.111.000027

DO - 10.1161/CIRCGENETICS.111.000027

M3 - Article

C2 - 24122612

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JO - Circulation. Genomic and precision medicine

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SN - 1942-325X

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