title: Association ofFURINandZPR1polymorphisms with metabolic syndrome.
abstract: Although genome-wide association studies (GWASs) have identified various genes and loci in predisposition to metabolic syndrome (MetS) or each component of this condition, the genetic basis of MetS in individuals remains to be identified definitively. The aim of the present study was to examine the possible association of MetS in individuals with 29 polymorphisms that were previously identified as susceptibility loci for coronary artery disease or myocardial infarction by meta-analyses of GWASs. The study population comprised 1,822 subjects with MetS and 1,096 controls. Subjects with MetS had ≥3 of the 5 components of the diagnostic criteria for MetS, whereas control individuals had 0-1 of the 5 components. The genotypes for the 29 polymorphisms were determined by the multiplex bead-based Luminex assay. Comparisons of allele frequencies by the χ2test revealed that rs17514846 (A→C) of the furin (paired basic amino acid-cleaving enzyme) gene (FURIN; P=0.0006), rs964184 (C→G) of the ZPR1 zinc finger gene (ZPR1; P=0.0078) and rs599839 (G→A) of the proline/serine-rich coiled-coil 1 gene (P=0.0486) were significantly (P<0.05) associated with the prevalence of MetS. Multivariable logistic regression analysis with adjustment for age, gender and smoking status revealed that rs17514846 ofFURIN(P=0.0016; odds ratio, 0.76; dominant model) and rs964184 ofZPR1(P=0.0164; odds ratio, 1.21; dominant model) were significantly associated with MetS. The minorAallele of rs17514846 ofFURINwas significantly associated with a decrease in the serum concentration of triglycerides (P=0.0293) and to an increase in the serum concentration of high-density lipoprotein (HDL) cholesterol (P=0.0460). The minorGallele of rs964184 ofZPR1was significantly associated with increases in the serum concentration of triglycerides (P=6.2×10-9) and fasting plasma glucose level (P=0.0028) and to a decrease in the serum concentration of HDL cholesterol (P=0.0105).FURINandZPR1may thus be susceptibility loci for MetS.
authors.affiliation: Department of Cardiovascular Medicine, Gifu Prefectural Tajimi Hospital, Tajimi, Gifu 507-8522, Japan.
authors.forename: Chikara
authors.initials: C
authors.lastname: Ueyama
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 Cardiovascular Medicine, Gifu Prefectural Tajimi Hospital, Tajimi, Gifu 507-8522, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Yamase
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 Internal Medicine, Meitoh Hospital, Nagoya, Aichi 465-0025, Japan.
authors.forename: Kimihiko
authors.initials: K
authors.lastname: Kato
authors.affiliation: Department of Cardiology, Gifu Prefectural General Medical Center, Gifu 500-8717, Japan.
authors.forename: Masazumi
authors.initials: M
authors.lastname: Arai
authors.affiliation: Department of Cardiology, Gifu Prefectural General Medical Center, Gifu 500-8717, Japan.
authors.forename: Sachiro
authors.initials: S
authors.lastname: Watanabe
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan.
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Murohara
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: diabetes mellitus; dyslipidemia; genetics; metabolic syndrome; polymorphism