Genetic Variants of <i>RAMP2</i> and <i>CLR</i> are Associated with Stroke

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Author(s)

    • Koyama Teruhide
    • Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine
    • Shimanoe Chisato
    • Department of Preventive Medicine, Faculty of Medicine, Saga University
    • Tanaka Keitaro
    • Department of Preventive Medicine, Faculty of Medicine, Saga University
    • Oze Isao
    • Division of Molecular and Clinical Epidemiology, Aichi Cancer Center Research Institute
    • Ito Hidemi
    • Division of Molecular and Clinical Epidemiology, Aichi Cancer Center Research Institute
    • Uemura Hirokazu
    • Department of Preventive Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School
    • Katsuura-Kamano Sakurako
    • Department of Preventive Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School
    • Ibusuki Rie
    • Department of International Islands and Community Medicine, Kagoshima University Graduate School of Medical and Dental Sciences
    • Shimoshikiryo Ippei
    • Department of International Islands and Community Medicine, Kagoshima University Graduate School of Medical and Dental Sciences
    • Kadota Aya
    • Department of Public Health, Shiga University of Medical Science|Center for Epidemiologic Research in Asia, Shiga University of Medical Science
    • Kuriyama Nagato
    • Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine
    • Kawai Sayo
    • Department of Preventive Medicine, Nagoya University Graduate School of Medicine
    • Sasakabe Tae
    • Department of Preventive Medicine, Nagoya University Graduate School of Medicine
    • Okada Rieko
    • Department of Preventive Medicine, Nagoya University Graduate School of Medicine
    • Hishida Asahi
    • Department of Preventive Medicine, Nagoya University Graduate School of Medicine
    • Naito Mariko
    • Department of Preventive Medicine, Nagoya University Graduate School of Medicine
    • Kuriki Kiyonori
    • Laboratory of Public Health, School of Food and Nutritional Sciences, University of Shizuoka
    • Endoh Kaori
    • Laboratory of Public Health, School of Food and Nutritional Sciences, University of Shizuoka
    • Furusyo Norihiro
    • Department of Environmental Medicine and Infectious Disease, Kyushu University
    • Ikezaki Hiroaki
    • Department of Environmental Medicine and Infectious Disease, Kyushu University
    • Suzuki Sadao
    • Department of Public Health, Nagoya City University Graduate School of Medical Sciences
    • Ozaki Etsuko
    • Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine
    • Hosono Akihiro
    • Department of Public Health, Nagoya City University Graduate School of Medical Sciences
    • Mikami Haruo
    • Cancer Prevention Center, Chiba Cancer Center Research Institute
    • Nakamura Yohko
    • Cancer Prevention Center, Chiba Cancer Center Research Institute
    • Kubo Michiaki
    • Laboratory for Genotyping Development, Center for Integrative Medical Sciences, RIKEN
    • Wakai Kenji
    • Department of Preventive Medicine, Nagoya University Graduate School of Medicine
    • Matsui Daisuke
    • Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine
    • Watanabe Isao
    • Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine
    • Takeshita Wakiko
    • Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine
    • Iwai Komei
    • Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine
    • Watanabe Yoshiyuki
    • Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine

Abstract

<p><b><i>Aim</i>:</b> Stroke is associated closely with vascular homeostasis, and several complex processes and interacting pathways, which involve various genetic and environmental factors, contribute to the risk of stroke. Although adrenomedullin (ADM) has a number of physiological and vasoprotective functions, there are few studies of the ADM receptor system in humans. The ADM receptor comprises a calcitonin-receptor-like receptor (CLR) and receptor activity-modifying proteins (RAMPs). We analyzed single nucleotide polymorphisms (SNPs) in the <i>RAMP2</i> and <i>CLR</i> genes to determine their association with stroke in the light of gene-environment interactions.</p><p><b><i>Methods</i>:</b> Using cross-sectional data from the Japan Multi-Institutional Collaborative Cohort Study in the baseline surveys, 14,087 participants from 12 research areas were genotyped. We conducted a hypothesis-based association between stroke prevalence and SNPs in the <i>RAMP2</i> and <i>CLR</i> genes based on data abstracted from two SNPs in <i>RAMP2</i> and 369 SNPs in <i>CLR</i>. We selected five SNPs from among the <i>CLR</i> variants (rs77035639, rs3815524, rs75380157, rs574603859, and rs147565266) and one <i>RAMP2</i> SNP (rs753152), which were associated with stroke, for analysis.</p><p><b><i>Results</i>:</b> Five of the SNPs (rs77035639, rs3815524, rs75380157, rs147565266, and rs753152) showed no significant association with obesity, ischemic heart disease, hypertension, dyslipidemia, and diabetes. In the logistic regression analysis, rs574603859 had a lower odds ratio (0.238; 95% confidence interval, 0.076–0.745, adjusted for age, sex, and research area) and the other SNPs had higher odds ratios for association with stroke.</p><p><b><i>Conclusions</i>:</b> This was the first study to investigate the relationships between ADM receptor genes (<i>RAMP2</i> and <i>CLR</i>) and stroke in the light of gene-environment interactions in human.</p>

Journal

  • Journal of Atherosclerosis and Thrombosis

    Journal of Atherosclerosis and Thrombosis 24(12), 1267-1281, 2017

    Japan Atherosclerosis Society

Codes

  • NII Article ID (NAID)
    130006235289
  • Text Lang
    ENG
  • ISSN
    1340-3478
  • Data Source
    J-STAGE 
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