title: Common dysfunctional variants in ABCG2 are a major cause of early-onset gout.
abstract: Gout is a common disease which mostly occurs after middle age, but more people nowadays develop it before the age of thirty. We investigated whether common dysfunction of ABCG2, a high-capacity urate transporter which regulates serum uric acid levels, causes early-onset gout. 705 Japanese male gout cases with onset age data and 1,887 male controls were genotyped, and the ABCG2 functions which are estimated by its genotype combination were determined. The onset age was 6.5 years earlier with severe ABCG2 dysfunction than with normal ABCG2 function (P = 6.14 × 10(-3)). Patients with mild to severe ABCG2 dysfunction accounted for 88.2% of early-onset cases (twenties or younger). Severe ABCG2 dysfunction particularly increased the risk of early-onset gout (odds ratio 22.2, P = 4.66 × 10(-6)). Our finding that common dysfunction of ABCG2 is a major cause of early-onset gout will serve to improve earlier prevention and therapy for high-risk individuals.
authors.affiliation: Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa, Saitama, Japan. hmatsuo@ndmc.ac.jp
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Matsuo
authors.forename: Kimiyoshi
authors.initials: K
authors.lastname: Ichida
authors.forename: Tappei
authors.initials: T
authors.lastname: Takada
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Nakayama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakashima
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nakamura
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kawamura
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Takada
authors.forename: Ken
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Hiroki
authors.initials: H
authors.lastname: Inoue
authors.forename: Yuji
authors.initials: Y
authors.lastname: Oikawa
authors.forename: Mariko
authors.initials: M
authors.lastname: Naito
authors.forename: Asahi
authors.initials: A
authors.lastname: Hishida
authors.forename: Kenji
authors.initials: K
authors.lastname: Wakai
authors.forename: Chisa
authors.initials: C
authors.lastname: Okada
authors.forename: Seiko
authors.initials: S
authors.lastname: Shimizu
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sakiyama
authors.forename: Toshinori
authors.initials: T
authors.lastname: Chiba
authors.forename: Hiraku
authors.initials: H
authors.lastname: Ogata
authors.forename: Kazuki
authors.initials: K
authors.lastname: Niwa
authors.forename: Makoto
authors.initials: M
authors.lastname: Hosoyamada
authors.forename: Atsuyoshi
authors.initials: A
authors.lastname: Mori
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hamajima
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Yoshikatsu
authors.initials: Y
authors.lastname: Kanai
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Sakurai
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Hosoya
authors.forename: Toru
authors.initials: T
authors.lastname: Shimizu
authors.forename: Nariyoshi
authors.initials: N
authors.lastname: Shinomiya
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D016022:Case-Control Studies; D006073:Gout / Q000235:genetics*; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D009363:Neoplasm Proteins