Journal of Atherosclerosis and Thrombosis
Online ISSN : 1880-3873
Print ISSN : 1340-3478
ISSN-L : 1340-3478
Original Article
Genetic Variants of RAMP2 and CLR are Associated with Stroke
Teruhide KoyamaNagato KuriyamaEtsuko OzakiDaisuke MatsuiIsao WatanabeWakiko TakeshitaKomei IwaiYoshiyuki WatanabeMasahiro NakatochiChisato ShimanoeKeitaro TanakaIsao OzeHidemi ItoHirokazu UemuraSakurako Katsuura-KamanoRie IbusukiIppei ShimoshikiryoNaoyuki TakashimaAya KadotaSayo KawaiTae SasakabeRieko OkadaAsahi HishidaMariko NaitoKiyonori KurikiKaori EndohNorihiro FurusyoHiroaki IkezakiSadao SuzukiAkihiro HosonoHaruo MikamiYohko NakamuraMichiaki KuboKenji Wakai
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2017 Volume 24 Issue 12 Pages 1267-1281

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Abstract

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.

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.

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.

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.

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この記事はクリエイティブ・コモンズ [表示 - 非営利 - 継承 4.0 国際]ライセンスの下に提供されています。
https://creativecommons.org/licenses/by-nc-sa/4.0/deed.ja
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