Genetic Variants of <i>RAMP2</i> and <i>CLR</i> are Associated with Stroke
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- Koyama Teruhide
- Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine
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- Kuriyama Nagato
- Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine
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- Ozaki Etsuko
- Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine
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- Matsui Daisuke
- Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine
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- Watanabe Isao
- Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine
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- Takeshita Wakiko
- Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine
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- Iwai Komei
- Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine
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- Watanabe Yoshiyuki
- Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine
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- Nakatochi Masahiro
- Center for Advanced Medicine and Clinical Research, Nagoya University Hospital
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- Shimanoe Chisato
- Department of Preventive Medicine, Faculty of Medicine, Saga University
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- Tanaka Keitaro
- Department of Preventive Medicine, Faculty of Medicine, Saga University
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- Oze Isao
- Division of Molecular and Clinical Epidemiology, Aichi Cancer Center Research Institute
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- Ito Hidemi
- Division of Molecular and Clinical Epidemiology, Aichi Cancer Center Research Institute
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- Uemura Hirokazu
- Department of Preventive Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School
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- Katsuura-Kamano Sakurako
- Department of Preventive Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School
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- Ibusuki Rie
- Department of International Islands and Community Medicine, Kagoshima University Graduate School of Medical and Dental Sciences
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- Shimoshikiryo Ippei
- Department of International Islands and Community Medicine, Kagoshima University Graduate School of Medical and Dental Sciences
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- Takashima Naoyuki
- Department of Public Health, Shiga University of Medical Science
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- Kadota Aya
- Department of Public Health, Shiga University of Medical Science Center for Epidemiologic Research in Asia, Shiga University of Medical Science
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- Kawai Sayo
- Department of Preventive Medicine, Nagoya University Graduate School of Medicine
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- Sasakabe Tae
- Department of Preventive Medicine, Nagoya University Graduate School of Medicine
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- Okada Rieko
- Department of Preventive Medicine, Nagoya University Graduate School of Medicine
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- Hishida Asahi
- Department of Preventive Medicine, Nagoya University Graduate School of Medicine
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- Naito Mariko
- Department of Preventive Medicine, Nagoya University Graduate School of Medicine
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- Kuriki Kiyonori
- Laboratory of Public Health, School of Food and Nutritional Sciences, University of Shizuoka
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- Endoh Kaori
- Laboratory of Public Health, School of Food and Nutritional Sciences, University of Shizuoka
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- Furusyo Norihiro
- Department of Environmental Medicine and Infectious Disease, Kyushu University
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- Ikezaki Hiroaki
- Department of Environmental Medicine and Infectious Disease, Kyushu University
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- Suzuki Sadao
- Department of Public Health, Nagoya City University Graduate School of Medical Sciences
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- Hosono Akihiro
- Department of Public Health, Nagoya City University Graduate School of Medical Sciences
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- Mikami Haruo
- Cancer Prevention Center, Chiba Cancer Center Research Institute
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- Nakamura Yohko
- Cancer Prevention Center, Chiba Cancer Center Research Institute
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- Kubo Michiaki
- Laboratory for Genotyping Development, Center for Integrative Medical Sciences, RIKEN
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- Wakai Kenji
- Department of Preventive Medicine, Nagoya University Graduate School of Medicine
Bibliographic Information
- Other Title
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- Genetic Variants of RAMP2 and CLR are Associated with Stroke
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Abstract
<p>Aim: 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 RAMP2 and CLR genes to determine their association with stroke in the light of gene-environment interactions.</p><p>Methods: 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 RAMP2 and CLR genes based on data abstracted from two SNPs in RAMP2 and 369 SNPs in CLR. We selected five SNPs from among the CLR variants (rs77035639, rs3815524, rs75380157, rs574603859, and rs147565266) and one RAMP2 SNP (rs753152), which were associated with stroke, for analysis.</p><p>Results: 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>Conclusions: This was the first study to investigate the relationships between ADM receptor genes (RAMP2 and CLR) and stroke in the light of gene-environment interactions in human.</p>
Journal
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- Journal of Atherosclerosis and Thrombosis
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Journal of Atherosclerosis and Thrombosis 24 (12), 1267-1281, 2017
Japan Atherosclerosis Society