TY - JOUR
T1 - Genetic variants of RAMP2 and CLR are associated with stroke
AU - Koyama, Teruhide
AU - Kuriyama, Nagato
AU - Ozaki, Etsuko
AU - Matsui, Daisuke
AU - Watanabe, Isao
AU - Takeshita, Wakiko
AU - Iwai, Komei
AU - Watanabe, Yoshiyuki
AU - Nakatochi, Masahiro
AU - Shimanoe, Chisato
AU - Tanaka, Keitaro
AU - Oze, Isao
AU - Ito, Hidemi
AU - Uemura, Hirokazu
AU - Katsuura-Kamano, Sakurako
AU - Ibusuki, Rie
AU - Shimoshikiryo, Ippei
AU - Takashima, Naoyuki
AU - Kadota, Aya
AU - Kawai, Sayo
AU - Sasakabe, Tae
AU - Okada, Rieko
AU - Hishida, Asahi
AU - Naito, Mariko
AU - Kuriki, Kiyonori
AU - Endoh, Kaori
AU - Furusyo, Norihiro
AU - Ikezaki, Hiroaki
AU - Suzuki, Sadao
AU - Hosono, Akihiro
AU - Mikami, Haruo
AU - Nakamura, Yohko
AU - Kubo, Michiaki
AU - Wakai, Kenji
N1 - Publisher Copyright:
© Japan Atherosclerosis Society.
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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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U2 - 10.5551/jat.41517
DO - 10.5551/jat.41517
M3 - Article
C2 - 28904253
AN - SCOPUS:85037041193
SN - 1340-3478
VL - 24
SP - 1267
EP - 1281
JO - Journal of atherosclerosis and thrombosis
JF - Journal of atherosclerosis and thrombosis
IS - 12
ER -
