A common variant of leucine-rich repeat-containing 16A (LRRC16A) gene is associated with gout susceptibility View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-01

AUTHORS

Masayuki Sakiyama, Hirotaka Matsuo, Seiko Shimizu, Toshinori Chiba, Akiyoshi Nakayama, Yuzo Takada, Takahiro Nakamura, Tappei Takada, Emi Morita, Mariko Naito, Kenji Wakai, Hiroki Inoue, Seishiro Tatsukawa, Junki Sato, Kazumi Shimono, Toshiaki Makino, Takahiro Satoh, Hiroshi Suzuki, Yoshikatsu Kanai, Nobuyuki Hamajima, Yutaka Sakurai, Kimiyoshi Ichida, Toru Shimizu, Nariyoshi Shinomiya

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. More... »

PAGES

1-4

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s13577-013-0081-8

DOI

http://dx.doi.org/10.1007/s13577-013-0081-8

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1044445146

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/24318514


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