Genetic Variants of RAMP2 and CLR are Associated with Stroke.
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.
['Koyama|Teruhide|T|', 'Kuriyama|Nagato|N|', 'Ozaki|Etsuko|E|', 'Matsui|Daisuke|D|', 'Watanabe|Isao|I|', 'Takeshita|Wakiko|W|', 'Iwai|Komei|K|', 'Watanabe|Yoshiyuki|Y|', 'Nakatochi|Masahiro|M|', 'Shimanoe|Chisato|C|', 'Tanaka|Keitaro|K|', 'Oze|Isao|I|', 'Ito|Hidemi|H|', 'Uemura|Hirokazu|H|', 'Katsuura-Kamano|Sakurako|S|', 'Ibusuki|Rie|R|', 'Shimoshikiryo|Ippei|I|', 'Takashima|Naoyuki|N|', 'Kadota|Aya|A|', 'Kawai|Sayo|S|', 'Sasakabe|Tae|T|', 'Okada|Rieko|R|', 'Hishida|Asahi|A|', 'Naito|Mariko|M|', 'Kuriki|Kiyonori|K|', 'Endoh|Kaori|K|', 'Furusyo|Norihiro|N|', 'Ikezaki|Hiroaki|H|', 'Suzuki|Sadao|S|', 'Hosono|Akihiro|A|', 'Mikami|Haruo|H|', 'Nakamura|Yohko|Y|', 'Kubo|Michiaki|M|', 'Wakai|Kenji|K|']
D015415:Biomarkers D058286:Calcitonin Receptor-Like Protein D015331:Cohort Studies D003430:Cross-Sectional Studies D005260:Female D005500:Follow-Up Studies D006801:Humans D008297:Male D008875:Middle Aged D020641:Polymorphism, Single Nucleotide D011379:Prognosis D058263:Receptor Activity-Modifying Protein 2 D020521:Stroke
Stroke Adrenomedullin Calcitonin-receptor-like receptor Receptor activity-modifying protein 2