title: Common variant of PDZ domain containing 1 (PDZK1) gene is associated with gout susceptibility: A replication study and meta-analysis in Japanese population.
abstract: PDZ domain containing 1 (PDZK1) is a scaffold protein that organizes a transportsome and regulates several transporters' functions including urate and drug transporters. Therefore, PDZK1 in renal proximal tubules may affect serum uric acid levels through PDZK1-binding renal urate transporters. Two previous studies in Japanese male population reported that a PDZK1 single nucleotide polymorphism (SNP), rs12129861, was not associated with gout. In the present study, we performed a further association analysis between gout and rs12129861 in a different large-scale Japanese male population and a meta-analysis with previous Japanese population studies. We genotyped rs12129861 in 1210 gout cases and 1224 controls of a Japanese male population by TaqMan assay. As a result, we showed that rs12129861 was significantly associated with gout susceptibility (P = 0.016, odds ratio [OR] = 0.80, 95% confidence interval [CI] 0.67-0.96). The result of the meta-analysis among Japanese populations also showed a significant association (P = 0.013, OR = 0.85, 95%CI 0.75-0.97). Our findings show the significant association between gout susceptibility and common variant of PDZK1 which reportedly regulates the functions of urate transporters in the urate transportsome.
authors.affiliation: Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa, Japan.
authors.forename: Toshihide
authors.initials: T
authors.lastname: Higashino
authors.affiliation: Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa, Japan. Electronic address: hmatsuo@ndmc.ac.jp.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Matsuo
authors.affiliation: Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sakiyama
authors.affiliation: Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa, Japan.
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Nakayama
authors.affiliation: Laboratory of Mathematics, National Defense Medical College, Tokorozawa, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Pharmacy, The University of Tokyo Hospital, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Tappei
authors.initials: T
authors.lastname: Takada
authors.affiliation: Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa, Japan.
authors.forename: Hiraku
authors.initials: H
authors.lastname: Ogata
authors.affiliation: Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kawamura
authors.affiliation: Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Kawaguchi
authors.affiliation: Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Naito
authors.affiliation: Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Sayo
authors.initials: S
authors.lastname: Kawai
authors.affiliation: Faculty of Medical Science, Teikyo University of Science, Tokyo, Japan.
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Takada
authors.affiliation: Ryougoku East Gate Clinic, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ooyama
authors.affiliation: Department of Pharmacy, The University of Tokyo Hospital, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa, Japan.
authors.forename: Nariyoshi
authors.initials: N
authors.lastname: Shinomiya
mesh_terms: D000328:Adult; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D006073:Gout / Q000235:genetics*; D006801:Humans; D007564:Japan; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; C484659:PDZK1 protein, human
keywords: Drug transportsome; PDZK1; Single nucleotide polymorphism; Urate transportsome; Uric acid