title: Association of a transcription factor 21 gene polymorphism with hypertension.
abstract: Various loci and genes that confer susceptibility to coronary artery disease (CAD) have been identified mainly in Caucasian populations by genome-wide association studies (GWASs). As hypertension is a major risk factor for CAD, certain polymorphisms may contribute to the genetic susceptibility to CAD through affecting the predisposition to hypertension. The aim of the present study was to examine a possible association of hypertension with 29 single-nucleotide polymorphisms (SNPs) previously identified by meta-analyses of GWASs as susceptibility loci for CAD. Study subjects comprised of 5,460 individuals (3,348 subjects with hypertension and 2,112 controls). The genotypes of SNPs were determined by the multiplex bead-based Luminex assay. The χ2test revealed that genotype distributions and allele frequencies for rs12190287 of the transcription factor 21 gene (TCF21) and rs1122608 of the SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 4 gene (SMARCA4) were significantly (P<0.05) associated with hypertension. Allele frequencies for rs9369640 of the phosphatase and actin regulator 1 gene (PHACTR1) and genotype distributions for rs599839 of the proline/serine-rich coiled-coil 1 gene (PSRC1) were also significantly associated with hypertension. Multivariable logistic regression analysis with adjustment for age, gender, body mass index and smoking status revealed that rs12190287 ofTCF21(P=0.0014; recessive model; odds ratio, 1.21) was significantly associated with hypertension, and theCallele represented a risk factor for this condition. Similar analyses revealed that rs1122608 ofSMARCA4(P=0.0305; dominant model; odds ratio, 0.86), rs9369640 ofPHACTR1(P=0.0119; dominant model; odds ratio, 0.82) and rs599839 ofPSRC1(P=0.0248; dominant model; odds ratio, 0.84) were also related to hypertension, with the minorT, CandGalleles, respectively, being protective against this condition. Thus, the present results indicate that rs12190287 (G→C) ofTCF21is a susceptibility locus for hypertension.
authors.affiliation: Department of Cardiovascular Medicine, Inabe General Hospital, Inabe, Mie 511-0428, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Fujimaki
authors.affiliation: Department of Cardiology, Japanese Red Cross Nagoya First Hospital, Nagoya, Aichi 453-8511, Japan.
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Oguri
authors.affiliation: Department of Cardiovascular Medicine, Gifu Prefectural Tajimi Hospital, Tajimi, Gifu 507-8522, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Horibe
authors.affiliation: Department of Internal Medicine, Meitoh Hospital, Nagoya, Aichi 465-0025, Japan ; Department of Human Functional Genomics, Life Science Research Center, Mie University, Tsu, Mie 514-8507, Japan.
authors.forename: Kimihiko
authors.initials: K
authors.lastname: Kato
authors.affiliation: Department of Cardiology, Gifu Prefectural General Medical Center, Gifu, Gigu 500-8717, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Matsuoka
authors.affiliation: Department of Cardiology, Gifu Prefectural General Medical Center, Gifu, Gigu 500-8717, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Abe
authors.affiliation: Department of Cardiology, Gifu Prefectural General Medical Center, Gifu, Gigu 500-8717, Japan.
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Tokoro
authors.affiliation: Department of Cardiology, Gifu Prefectural General Medical Center, Gifu, Gigu 500-8717, Japan.
authors.forename: Masazumi
authors.initials: M
authors.lastname: Arai
authors.affiliation: Department of Cardiology, Gifu Prefectural General Medical Center, Gifu, Gigu 500-8717, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Noda
authors.affiliation: Department of Cardiology, Gifu Prefectural General Medical Center, Gifu, Gigu 500-8717, Japan.
authors.forename: Sachiro
authors.initials: S
authors.lastname: Watanabe
authors.affiliation: Department of Human Functional Genomics, Life Science Research Center, Mie University, Tsu, Mie 514-8507, Japan.
authors.forename: Yoshiji
authors.initials: Y
authors.lastname: Yamada
keywords: TCF21; cardiovascular disease; genetics; hypertension; polymorphism