Gout is a self-limited inflammatory joint disease which pathogenesis is complex and it attack is the outcome of combined action of multiple factors.Such as excessive intake sea food or alcohol is considered the predominant risk factor of gout,and the result from Horvathova V et al revealed that as the increase of the age,the risk of gout is also increasely and the gout patients compare to healthy individuals have higher BMIs.Studies have shown that[16–18] there are close correlations between gout and kidney disease,obesity,hypertension,diabetes mellitus,cardiovascular and cerebrovascular diseases and so on.Our analysis showing that BMI,DBP,SUA,GLU,BUN,CREA,TG,HDL-C and LDL-C are the risk factors of gout which in line with most of the research conclusion[19–20].However,in particular,gout is a polygenic hereditary disease and genetic factors are still play crucial role in gout.
NLRP3 belongs to NOD-like receptor protein family which as pattern-recognition receptors,in order to identify danger signals of endogenous and exogenous,participate the processing and secretion of inflammatory cytokines,to induced the inflammation or apoptosis in cell eventually.MSU crystals can effectively activation the NLRP3 inflammasome as irritant.To begin with,it can act on NLRP3 protein in macrophages,activation Leucine repeat (LRR) at the C-terminus of NLRP3 protein;then recruiting apoptotic-related spot-like protein(ASC) by pyrin domain (PYD) area of NLRP3 protein;at that time,ASC through interaction of caspase recruitment domains prompt pro-caspase-1 into the activation of caspase-1.The activation of caspase-1 can pyrolysis pro-IL-1β,make it convert to mature bioactive IL-1β and release to extracellular which cause inflammation[21–23].There are many pathogenesis of gout,but some scholars believe that MSU crystals stimulus NLRP3 protein lead to the release of IL-1β have a crucial role in gout.And increasing evidence indicates that[24–26] NLPR3 participate the onset of gout,diabetes,rheumatoid arthritis,systemic lupus erythematosus,Sjogren's syndrome,atherosclerosis,autoinflammatory syndromes and so on.
IL-1β is a kind of pro-inflammatory cytokines,to a certain extent,production and release of IL-1β can resistance infection,but at the same time,there are correlations with gout,rheumatoid arthritis,chronic kidney disease,atherosclerosis and so on[27–28].Studies have demonstrated that IL-1β can promote the recruitment of neutrophil in the part of inflammation so that cause gout.In addition,IL-1β can make the person produces strong pain by activation injured receptor which exist in peripheral sensory nerve system sensitively and directly.The processing and secretion of IL-1β not only can through NOD-like receptor signaling pathways,but also can by Toll-like receptor signaling pathways.When MSU crystals are identified by Toll-like receptor,TLRs are able to interact with MyD88,make the MyD88 activation,leading to the activation of nuclear factor kappa B (NF-κB) and enter the nucleus to produce IL-1β,cause inflammation eventually through the cascade amplification effect[30–31].
The associations between NLRP3 and IL-1β gene polymorphisms and diseases susceptibility have been studied.The results from a meta-analysis of Lee YH et al have revealed that rs10754558 of NLRP3 gene variant was no association with autoimmune and inflammatory diaeases.There was correlation between rs3806268 of NLRP3 gene polymorphism and nontuberculous mycobacteria lung disease in female by Wu MF et al.And studies have observed that rs16944 loci variant of IL-1β gene has no association with breast cancer but rs1143634 carriers T allele may reduced the risk of rheumatoid arthritis[34–35].Our results found that the distribution of genotype and allele frequency in rs3806268 of NLRP3 gene and rs1143634 of IL-1β gene had significant differences in gout patients and controls(P༜0.05),and further explore discovered that NLRP3 gene rs3806268 loci AA genotype and rs1143634 of IL-1β gene AA + GA genotype was protective factors for gout(95%CI༜1).Our results were consistent with Deng J et al and Wang LF et al,but did not agree with the result of Zhang QB et al[36–38].
This research is still exist some limitations,summarized as followed:(1)Sample size is not big enough and the object of this study are collected from the same hospital;(2)This research is a case control study,but more prospective studies are necessary in the future;(3)This study did not consider geographical factors,thus the results can not promotion widely;(4)If this study gain the detection of the cytokine and mRNA level,the results may be more persuasive.