TNFAIP3 Gene Polymorphisms in Three Common Autoimmune Diseases: Systemic Lupus Erythematosus, Rheumatoid Arthritis, and Primary Sjogren Syndrome-Association with Disease Susceptibility and Clinical Phenotypes in Italian Patients
TNFAIP3 Gene Polymorphisms in Three Common Autoimmune Diseases: Systemic Lupus Erythematosus, Rheumatoid Arthritis, and Primary Sjogren Syndrome-Association with Disease Susceptibility and Clinical Phenotypes in Italian Patients
复制标题
DOI：
10.1155/2019/6728694
复制
发表时间：
2019-08-27
影响因子：
4.1
通讯作者：
Borgiani, P.
中科院分区：
文献类型：
--
作者：
Ciccacci, C.;Latini, A.;Borgiani, P.
自身免疫性疾病（Autoimmune diseases，AIDS）是一种以持续性或复发性炎症、免疫应答改变和特异性自身抗体产生为特征的复杂疾病。已知不同的艾滋病共享几个易感性遗传基因座。肿瘤坏死因子α诱导蛋白3（TNFAIP 3）编码泛素修饰酶A20，其通过限制NF-κ B（一种调节各种促炎基因表达的转录因子）来下调炎症。TNFAIP 3基因的变异与几种艾滋病的易感性有关。在这里，我们分析了两个TNFAIP 3多态性在意大利患者的系统性红斑狼疮（SLE），类风湿性关节炎（RA），原发性干燥综合征（pSS），以验证TNFAIP 3基因的遗传变异性是否参与遗传易感性艾滋病也在意大利人口。我们招募了313名SLE患者、256名RA患者、195名pSS患者和236名健康对照。采用等位基因识别法对TNFAIP 3基因rs 2230926和rs6920220进行基因分型。我们进行了病例/对照关联研究和基因型/表型相关分析。观察到rs 2230926发生SLE的风险更高（P=0.02，OR=1.92）。未观察到该SNP与pSS或RA的易感性之间存在关联。然而，rs 2230926变异等位基因似乎赋予pSS患者更高的发展淋巴瘤的风险，而在RA患者中，RF的存在与变异等位基因显著相关。对于rs6920220 SNP，我们观察到该变异等位基因与SLE（P=0.03，OR=1.53）、pSS（P=0.016，OR=1.69）和RA（P=0.0001，OR=2.35）易感性显著相关。此外，SLE患者携带变异等位基因表现出更高的风险，发展心包炎，胸膜炎，肾脏并发症。我们的研究结果支持了TNFAIP 3基因变异体在意大利人群中不同自身免疫性疾病发展中的重要作用，并进一步证实了这三种病理之间遗传易感因素的共享。
Autoimmune diseases (AIDs) are complex diseases characterized by persistent or recurrent inflammation, alteration of immune response, and production of specific autoantibodies. It is known that different AIDs share several susceptibility genetic loci. Tumor necrosis factor alpha inducible protein 3 (TNFAIP3) encodes the ubiquitin-modifying enzyme A20, which downregulates inflammation by restricting NF-kappa B, a transcription factor that regulates expression of various proinflammatory genes. Variants in TNFAIP3 gene have been described as associated with susceptibility to several AIDs. Here, we analyzed two TNFAIP3 polymorphisms in Italian patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and primary Sjogren's syndrome (pSS), to verify if the genetic variability of TNFAIP3 gene is involved in genetic predisposition to AIDs also in the Italian population. We recruited 313 SLE patients, 256 RA patients, 195 pSS patients, and 236 healthy controls. Genotyping of rs2230926 and rs6920220 in TNFAIP3 gene was performed by an allelic discrimination assay. We carried out a case/control association study and a genotype/phenotype correlation analysis. A higher risk to develop SLE was observed for rs2230926 (P=0.02, OR=1.92). No association was observed between this SNP and the susceptibility to pSS or RA. However, the rs2230926 variant allele seems to confer a higher risk to develop lymphoma in pSS patients, while in RA patients, the presence of RF resulted significantly associated with the variant allele. Regarding the rs6920220 SNP, we observed a significant association of the variant allele with SLE (P=0.03, OR=1.53), pSS (P=0.016, OR=1.69), and RA (P=0.0001, OR=2.35) susceptibility. Furthermore, SLE patients carrying the variant allele showed a higher risk to develop pericarditis, pleurisy, and kidney complications. Our results support the importance of the TNFAIP3 gene variant role in the development of different autoimmune diseases in the Italian population and furtherly confirm a sharing of genetic predisposing factors among these three pathologies.