Genetic variants of RAMP2 and CLR are associated with stroke

Teruhide Koyama, Nagato Kuriyama, Etsuko Ozaki, Daisuke Matsui, Isao Watanabe, Wakiko Takeshita, Komei Iwai, Yoshiyuki Watanabe, Masahiro Nakatochi, Chisato Shimanoe, Keitaro Tanaka, Isao Oze, Hidemi Ito, Hirokazu Uemura, Sakurako Katsuura-Kamano, Rie Ibusuki, Ippei Shimoshikiryo, Naoyuki Takashima, Aya Kadota, Sayo KawaiTae Sasakabe, Rieko Okada, Asahi Hishida, Mariko Naito, Kiyonori Kuriki, Kaori Endoh, Norihiro Furusyo, Hiroaki Ikezaki, Sadao Suzuki, Akihiro Hosono, Haruo Mikami, Yohko Nakamura, Michiaki Kubo, Kenji Wakai

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1267-1281
Number of pages15
JournalJournal of atherosclerosis and thrombosis
Volume24
Issue number12
DOIs
Publication statusPublished - 2017

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Cardiology and Cardiovascular Medicine
  • Biochemistry, medical

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