Associations of functional NLRP3 polymorphisms with susceptibility to food-induced anaphylaxis and aspirin-induced asthma
Associations of functional NLRP3 polymorphisms with susceptibility to food-induced anaphylaxis and aspirin-induced asthma
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DOI：
10.1016/j.jaci.2009.07.044
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发表时间：
2009-10-01
影响因子：
14.2
通讯作者：
Tamari, Mayumi
中科院分区：
文献类型：
--
作者：
Hitomi, Yuki;Ebisawa, Motohiro;Tamari, Mayumi
背景：NLR家族pyrin domain containing 3 （NLRP3）通过形成炎性小体来控制炎性caspase-1的活性，从而导致原细胞因子IL-1 β和IL-18的分裂。最近的研究表明，人类NLRP3多态性与各种炎症性疾病的易感性有关；然而，与过敏性疾病的关系尚不清楚。目的：我们试图研究NLRP3多态性是否与食物过敏、食物诱发性过敏反应和阿司匹林诱发哮喘（AIA）的易感性相关。方法：选取NLRP3的15个标签单核苷酸多态性（snp），分别对574份食物过敏样本和1279份AIA样本进行NLRP3相关性分析。我们进一步对易感snp进行了功能分析。结果：两个NLRP3 snp （rs4612666和rs10754558）与食物过敏性反应易感性显著相关（P = 0.00086和P = 0.00068）。2个snp的NLRP3单倍型也显示出显著的相关性（P = 0.000098）。我们可以证实与另一种超敏表型AIA的易感性相关（rs4612666, P = 0.0096）。功能分析显示，rs4612666和rs10754558风险等位基因分别增加了NLRP3表达增强子活性和NLRP3 mRNA稳定性。结论：NLRP3 snp可能以功能获得的方式在食物性过敏反应和AIA的发生发展中发挥重要作用。对NLRP3炎症小体的进一步研究将有助于开发新的食物性过敏反应和AIA的诊断和治疗方法。[J] .中华过敏症杂志，2009;24:779-85。
Background: NLR family, pyrin domain containing 3 (NLRP3), controls the activity of inflammatory caspase-1 by forming inflammasomes, which leads to cleavage of the procytokines IL-1 beta and IL-18. Recent studies have shown associations of human NLRP3 polymorphisms with susceptibility to various inflammatory diseases; however, the association with allergic diseases remains unclear.Objective: We sought to examine whether NLRP3 polymorphisms are associated with susceptibility to food allergy, food-induced anaphylaxis, and aspirin-induced asthma (AIA).Methods: We selected 15 tag single nucleotide polymorphisms (SNPs) of NLRP3 and conducted association analyses of NLRP3 using 574 and 1279 samples for food allergy and AIA, respectively. We further performed functional analyses of the susceptible SNPs.Results: Two NLRP3 SNPs (rs4612666 and rs10754558) were significantly associated with susceptibility to food-induced anaphylaxis (P = .00086 and P = .00068, respectively). The NLRP3 haplotype of the 2 SNPs also showed a significant association (P = .000098). We could confirm the association with susceptibility to another hypersensitivity phenotype, AIA (rs4612666, P = .0096). Functional analysis revealed that the risk alleles of rs4612666 and rs10754558 increased the enhancer activity of NLRP3 expression and NLRP3 mRNA stability, respectively.Conclusion: Our results indicate that the NLRP3 SNPs might play an important role in the development of food-induced anaphylaxis and AIA in a gain-of-function manner. Further research on the NLRP3 inflammasome will contribute to the development of novel diagnostic and therapeutic methods for food-induced anaphylaxis and AIA. (J Allergy Clin Immunol 2009;124:779-85.)