NALP3 inflammasome functional polymorphisms and gout susceptibility.
Gout is the most common autoinflammatory arthritis characterized by elevated serum urate and recurrent attacks of intra-articular crystal deposition of monosodium urate (MSU). Although the pathogenesis of gout is still unclear, accumulated studies indicate that genetic factors trigger gout development, including some susceptibility genes that control the production and clearance of urate and lead to hyperuricemia. However, the epidemiological evidence suggests that only less than 10% of hyperuricemia patients develop gout, indicating that other genes unrelated to the urate metabolism may also contribute to the diseases susceptibility. Accumulated evidences have implied that MSU crystal-induced inflammation is a paradigm of innate immunity and that NALP3 inflammasome, an innate immune complex containing NALP3, ASC and CARD-8, is involved in gout development. Recent studies suggest that NALP3 and CARD-8 functional mutations contribute to the development of autoinflammatory diseases including hereditary periodic fever syndrome, arthritis as well as hypertension susceptibility. Taking into account these genetic findings, here we would like to propose a novel hypothesis that functional mutations in NALP3 inflammasome may make NALP3 inflammasome as attractive susceptibility candidates and genetic markers for gout. Further clinical genetic studies need to be performed to confirm the role of NALP3 inflammasome in the etiology of gout.
Miao
Zhi-Min
ZM
Department of Medicine, the Affiliated Hospital of Qingdao Medical College, Qingdao University, Qingdao, P.R. China. miaozm@qdumh.qd.sd.cn
Zhao
Shi-Hua
SH
Yan
Sheng-Li
SL
Li
Chang-Gui
CG
Wang
Yan-Gang
YG
Meng
Dong-Mei
DM
Zhou
Li
L
Mi
Qing-Sheng
QS
D002352:Carrier Proteins / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006073:Gout / Q000235:genetics*; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D053583:Interleukin-1beta / Q000378:metabolism; D011110:Polymorphism, Genetic; D014527:Uric Acid / Q000378:metabolism
D002352:Carrier Proteins; D053583:Interleukin-1beta; D014527:Uric Acid