title: Common variant of leucine-rich repeat-containing 16A (LRRC16A) gene is associated with gout susceptibility.
abstract: Gout is a common disease resulting from hyperuricemia which causes acute arthritis. Recently, genome-wide association studies revealed an association between serum uric acid levels and a common variant of leucine-rich repeat-containing 16A (LRRC16A) gene. However, it remains to be clarified whether LRRC16A contributes to the susceptibility to gout. In this study, we investigated the relationship between rs742132 in LRRC16A and gout. A total of 545 Japanese male gout cases and 1,115 male individuals as a control group were genotyped. rs742132 A/A genotype significantly increased the risk of gout, conferring an odds ratio of 1.30 (95 % CI 1.05-1.60; p = 0.015). LRRC16A encodes a protein called capping protein ARP2/3 and myosin-I linker (CARMIL), which serves as an inhibitor of the actin capping protein (CP). CP is an essential element of the actin cytoskeleton, which binds to the barbed end of the actin filament and regulates its polymerization. In the apical membrane of proximal tubular cells in the human kidney, the urate-transporting multimolecular complex (urate transportsome) is proposed to consist of several urate transporters and scaffolding proteins, which interact with the actin cytoskeleton. Thus, if there is a CARMIL dysfunction and regulatory disability in actin polymerization, urate transportsome may be unable to operate appropriately. We have shown for the first time that CARMIL/LRRC16A was associated with gout, which could be due to urate transportsome failure.
authors: Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan.
authors: Masayuki
authors: M
authors: Sakiyama
authors: Hirotaka
authors: H
authors: Matsuo
authors: Seiko
authors: S
authors: Shimizu
authors: Toshinori
authors: T
authors: Chiba
authors: Akiyoshi
authors: A
authors: Nakayama
authors: Yuzo
authors: Y
authors: Takada
authors: Takahiro
authors: T
authors: Nakamura
authors: Tappei
authors: T
authors: Takada
authors: Emi
authors: E
authors: Morita
authors: Mariko
authors: M
authors: Naito
authors: Kenji
authors: K
authors: Wakai
authors: Hiroki
authors: H
authors: Inoue
authors: Seishiro
authors: S
authors: Tatsukawa
authors: Junki
authors: J
authors: Sato
authors: Kazumi
authors: K
authors: Shimono
authors: Toshiaki
authors: T
authors: Makino
authors: Takahiro
authors: T
authors: Satoh
authors: Hiroshi
authors: H
authors: Suzuki
authors: Yoshikatsu
authors: Y
authors: Kanai
authors: Nobuyuki
authors: N
authors: Hamajima
authors: Yutaka
authors: Y
authors: Sakurai
authors: Kimiyoshi
authors: K
authors: Ichida
authors: Toru
authors: T
authors: Shimizu
authors: Nariyoshi
authors: N
authors: Shinomiya
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D006073:Gout / Q000235:genetics*; D006801:Humans; D008297:Male; D008840:Microfilament Proteins; D027361:Organic Anion Transporters / Q000235:genetics / Q000502:physiology; D058105:Polymerization; D014527:Uric Acid / Q000097:blood / Q000378:metabolism
chemical_list: D000199:Actins; C547525:CARMIL1 protein, human; D002352:Carrier Proteins; D008840:Microfilament Proteins; D027361:Organic Anion Transporters; C103862:urate transporter; D014527:Uric Acid