title: Accumulation of common polymorphisms is associated with development of hypertension: a 12-year follow-up from the Ohasama study.
abstract: Hypertension is a complex multi-factorial and polygenic disorder. Nevertheless, most studies have focused on single-gene effects. Furthermore, a majority of these studies have been cross-sectional and diagnosed hypertension using conventional blood pressure (BP) measurements, which are known to be subject to biases, including the so-called white-coat effect. Thus, we performed a longitudinal association study to clarify the effects of polymorphism accumulation on the development of hypertension that is defined on the basis of self-measured BP at home (home BP). In 403 Japanese aged 40-79 years with home normotension (home BP <135/85 mm Hg, and not treated with antihypertensive medication at baseline), we examined the associations of 51 single-nucleotide polymorphisms (SNPs) classically nominated or reported to be associated with hypertension in the Japanese Millennium Genome Project for Hypertension with a 12-year risk of progression to home hypertension (home BP >or=135/85 mm Hg, or start of antihypertensive medication). Out of 51 SNPs, four significantly and independently predicted the risk of progression of home hypertension, even after adjustment for possible confounding factors, including baseline home BP value. These were rs3767489 near the regulator of G-protein signaling 2 (RGS2), rs4961 in adducin 1 (ADD1), rs2236957 in the calcium channel, voltage-dependent, alpha-2/delta-subunit 2 (CACNA2D2) and rs769214 in catalase (CAT). Accumulation of these SNPs significantly improved the predictive values for the development of home hypertension. In conclusion, this longitudinal study, which was based on home BP measurement, showed that accumulation of common polymorphisms reliably predicted the risk of future hypertension in the Japanese general population.
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Tohoku University, Sendai, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Hirohito
authors.initials: H
authors.lastname: Metoki
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Ohkubo
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Katsuya
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Tabara
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kikuya
authors.forename: Takuo
authors.initials: T
authors.lastname: Hirose
authors.forename: Ken
authors.initials: K
authors.lastname: Sugimoto
authors.forename: Kei
authors.initials: K
authors.lastname: Asayama
authors.forename: Ryusuke
authors.initials: R
authors.lastname: Inoue
authors.forename: Azusa
authors.initials: A
authors.lastname: Hara
authors.forename: Taku
authors.initials: T
authors.lastname: Obara
authors.forename: Jun
authors.initials: J
authors.lastname: Nakura
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Kohara
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Totsune
authors.forename: Toshio
authors.initials: T
authors.lastname: Ogihara
authors.forename: Hiromi
authors.initials: H
authors.lastname: Rakugi
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Miki
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Imai
mesh_terms: D000328:Adult; D000368:Aged; D015220:Calcium Channels / Q000235:genetics; D002148:Calmodulin-Binding Proteins / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D020710:RGS Proteins / Q000235:genetics; D000099291:Adducins
chemical_list: D015220:Calcium Channels; D002148:Calmodulin-Binding Proteins; D020710:RGS Proteins; D000099291:Adducins; C425903:CACNA2D1 protein, human; C087182:RGS2 protein, human