Single nucleotide polymorphisms at the TNFAIP3/A20 locus and susceptibility/resistance to inflammatory and autoimmune diseases.
Single nucleotide polymorphisms at the TNFAIP3/A20 locus and susceptibility/resistance to inflammatory and autoimmune diseases.
复制标题
TNFAIP3/A20 位点的单核苷酸多态性以及对炎症和自身免疫性疾病的易感性/抵抗力。
DOI：
10.1007/978-1-4939-0398-6_10
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发表时间：
2014
影响因子：
--
通讯作者：
Ferran,Christiane
中科院分区：
文献类型：
--
作者：
Mele,Alessandra;Cervantes,JesusRevuelta;Chien,Victor;Friedman,David;Ferran,Christiane
The anti-inflammatory and immune regulatory functions of the ubiquitin-editing and Nf-κB inhibitory protein A20 are well documented in vitro, and in multiple animal models. The high rank held by A20 in the cell’s physiologic anti-inflammatory defense mechanisms is highlighted by the striking phenotype of A20 knockout mice, characterized by cachexia, multi-organ failure, and premature death. Even partial depletion of A20, as inA20 heterozygous mice, significantly alters NF-κB activation in response to pro-inflammatory activators, even though these mice are phenotypically unremarkable at baseline. A recent burst of genome wide association studies (GWAS), fueled by advances in genomic technologies and analysis tools, uncovered associations between single nucleotide polymorphisms (SNPs) at theTNFAIP3/A20gene locus and multiple autoimmune and inflammatory diseases in humans. Interestingly, some of these studies emphasized significant associations betweenTNFAIP3/A20SNPs imparting decreased expression or loss of NF-κB inhibitory function, and susceptibility to systemic lupus erythematosus (SLE) and coronary artery disease (CAD). These clinical data phenocopy partial loss of A20 in mouse models of inflammatory diseases, thereby incriminatingTNFAIP3/A20deficiency as a pathogenic culprit in autoimmune and inflammatory diseases. In this chapter, we undertook a thorough review of studies that explored association betweenTNFAIP3/A20SNPs and human autoimmune and inflammatory diseases. Beyond the prognostic value ofTNFAIP3/A20SNPs for assessing disease risk, their implication in the pathogenic processes of these maladies prompts the pursuit of A20-targeted therapies for disease prevention/treatment in patients harboring susceptibility haplotypes.
