title: Influence of adrenomedullin 2/intermedin gene polymorphism on blood pressure, renal function and silent cerebrovascular lesions in Japanese: the Ohasama study.
abstract: Adrenomedullin 2/intermedin (AM2/IMD) is a novel vasodilator peptide with various effects on the renal function and cardiovascular system. An exonic insertion (I)/deletion (D) polymorphism (rs3840963) may influence generation of AM2/IMD-53, due to its location within the N-terminal sequence. We investigated the association of this polymorphism with blood pressure, renal function and the risk of silent cerebrovascular lesions in a Japanese population recruited from the Ohasama study. We recorded 24 h ambulatory blood pressure (ABP), estimated glomerular filtration rate (eGFR) and proteinuria of 1073 individuals over 40 years of age. Silent cerebrovascular lesions (lacunar infarction and white matter hyperintensity (WMH)) were recorded in 794 individuals over 55 years of age. Chronic kidney disease (CKD) was diagnosed in individuals with proteinuria and/or decreased eGFR ≤60 ml min(-1) per 1.73 m(2). DD carriers, compared with II and ID carriers, displayed significantly higher 24 h ABP (127.4 vs. 122.0 and 122.9 mm Hg, respectively, in systolic ABP, P=0.009; and 74.8 vs. 71.3 and 72.5 mm Hg, respectively, in diastolic ABP, P=0.002), and lower eGFR (75.4 vs. 82.6 and 82.9 ml min(-1) per 1.73 m(2), respectively, P=0.04). DD carriers also had a significantly higher odds ratio (OR) for prevalence of CKD (OR: 2.7, P=0.003), presence of lacunar infarction (OR: 2.4, P=0.01) and WMH (OR: 2.7, P=0.003), compared with II carriers. The AM2/IMD I/D polymorphism is associated with renal dysfunction, blood pressure regulation and asymptomatic cerebrovascular diseases in the Japanese general population.
authors.affiliation: Department of Planning for Drug Development and Clinical Evaluation, Tohoku University Graduate School of Pharmaceutical Sciences and Medicine, Aoba-ku, Sendai, Japan. hirose-t@med.tohoku.ac.jp
authors.forename: Takuo
authors.initials: T
authors.lastname: Hirose
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Totsune
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Nakashige
authors.forename: Hirohito
authors.initials: H
authors.lastname: Metoki
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kikuya
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Ohkubo
authors.forename: Azusa
authors.initials: A
authors.lastname: Hara
authors.forename: Michihiro
authors.initials: M
authors.lastname: Satoh
authors.forename: Ryusuke
authors.initials: R
authors.lastname: Inoue
authors.forename: Kei
authors.initials: K
authors.lastname: Asayama
authors.forename: Takeo
authors.initials: T
authors.lastname: Kondo
authors.forename: Kei
authors.initials: K
authors.lastname: Kamide
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Katsuya
authors.forename: Toshio
authors.initials: T
authors.lastname: Ogihara
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Izumi
authors.forename: Hiromi
authors.initials: H
authors.lastname: Rakugi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Takahashi
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Imai
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001794:Blood Pressure / Q000235:genetics*; D002561:Cerebrovascular Disorders / Q000235:genetics*; D016001:Confidence Intervals; D004247:DNA / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D005919:Glomerular Filtration Rate / Q000235:genetics; D006801:Humans; D007564:Japan / Q000453:epidemiology; D007668:Kidney / Q000502:physiology*; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D036361:Peptide Hormones / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011507:Proteinuria / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012306:Risk; D012424:Rural Population; D055815:Young Adult
chemical_list: C484330:ADM2 protein, human; D036361:Peptide Hormones; D012333:RNA, Messenger; D004247:DNA