title: Association of sixty-one non-synonymous polymorphisms in forty-one hypertension candidate genes with blood pressure variation and hypertension.
abstract: We previously selected a group of hypertension candidate genes by a key word search using the OMIM database of NCBI and validated 525 coding single nucleotide polymorphisms (SNPs) in 179 hypertension candidate genes by DNA sequencing in a Japanese population. In the present study, we examined the association between 61 non-synonymous SNPs and blood pressure variations and hypertension. We used DNA samples taken from 1,880 subjects in the Suita study, a population-based study using randomly selected subjects. Analyses of covariance adjusting for age, body mass index, hyperlipidemia, diabetes, smoking, drinking, and antihypertensive medication revealed that 17 polymorphisms in 16 genes (APOB, CAST, CLCNKB, CTNS, GHR, GYS1, HF1, IKBKAP, KCNJ11, LIPC, LPL, P2RY2, PON2, SLC4A1, TRH, VWF) were significantly associated with blood pressure variations. Multivariate logistic regression analysis with adjustment for the same factors revealed that 11 polymorphisms in 11 genes (CAST, CTLA4, F5, GC, GHR, LIPC, PLA2G7, SLC4A1, SLCI8A1, TRH, VWF) showed significant associations with hypertension. Five polymorphisms in five genes, CAST(calpastatin), LIPC (hepatic lipase), SLC4A1 (band 3 anion transporter), TRH (thyrotropin-releasing hormone), and VWF (von Willebrand factor), were significantly associated with both blood pressure variation and hypertension. Thus, our study suggests that these five genes were susceptibility genes for essential hypertension in this Japanese population.
authors.affiliation: Division of Preventive Cardiology, National Cardiovascular Center, Suita, Japan. ykokubo@hsp.ncvc.go.jp
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kokubo
authors.forename: Hitonobu
authors.initials: H
authors.lastname: Tomoike
authors.forename: Chihiro
authors.initials: C
authors.lastname: Tanaka
authors.forename: Mariko
authors.initials: M
authors.lastname: Banno
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Okuda
authors.forename: Nozomu
authors.initials: N
authors.lastname: Inamoto
authors.forename: Kei
authors.initials: K
authors.lastname: Kamide
authors.forename: Yuhei
authors.initials: Y
authors.lastname: Kawano
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Miyata
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics; D001794:Blood Pressure / Q000235:genetics*; D005260:Female; D005838:Genotype; D006304:Health Status; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA