Association between inflammasome-related polymorphisms and psoriatic arthritis
Association between inflammasome-related polymorphisms and psoriatic arthritis
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DOI：
10.1080/03009742.2020.1834611
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发表时间：
2020-12-09
影响因子：
2.1
通讯作者：
Alenius, G-M
中科院分区：
文献类型：
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作者：
Juneblad, K.;Kastbom, A.;Alenius, G-M
目的：银屑病关节炎（Psoriatic arthritis, PsA）是一种与银屑病相关的异质性炎症性疾病。潜在的遗传因素被认为是PsA疾病表达和预后的重要因素。白细胞介素-1 β调节蛋白复合物称为炎症小体，与几种炎症性疾病有关，如类风湿关节炎和牛皮癣。目的是确定炎症小体相关的遗传变异是否与PsA易感性或不同的疾病表型相关。方法：分析来自瑞典北部724例PsA患者和587例人群对照的DNA，检测NLRP3- q750k （rs35829419）、NLRP3 （rs10733113）、CARD8-C10X （rs2043211）、NLRP1 （rs8079034）和NLRP1 （rs878329）的单核苷酸多态性。结果：PsA患者与对照组相比，rs2043211基因型AA （vs AT+TT）与PsA患者存在显著相关性[优势比（OR）， 95%可信区间（CI） 1.32 (1.05-1.65), p = 0.016]；和rs878329 C-allele之间的轴向PsA的参与(或1.37 (95% CI) (1.02 - -1.84), p = 0.035), rs8079034 T-allele与传统合成疾病修饰风湿性关节炎药物的处方(或1.76 (95% CI) (1.23 - -2.53), p = 0.0020), rs10733113 G-allele和皮肤疾病患者早期发病(或1.58 (95% CI) (1.13 - -2.21), p = 0.007),和C-allele rs35829419和破坏性的疾病/变形(或1.63 (95% CI) (1.04 - -2.55), p = 0.030)。结论：本研究首次显示炎症小体相关基因CARD8-C10X （rs2043211）在PsA患者中与遗传多态性相关。PsA的不同表型与炎性小体基因的不同多态性之间的关联也被发现。我们的研究结果表明炎症小体基因参与了PsA的发病机制和疾病表达。
Objective: Psoriatic arthritis (PsA) is a heterogeneous inflammatory disease associated with psoriasis. Underlying genetic factors are considered important for disease expression and prognosis of PsA. Interleukin-1 beta-regulating protein complexes called inflammasomes are associated with several inflammatory diseases, e.g. rheumatoid arthritis and psoriasis. The aim was to determine whether inflammasome-related genetic variation is associated with PsA susceptibility or different disease phenotypes.Method: DNA from 724 patients with PsA and 587 population-based controls from northern Sweden was analysed for single-nucleotide polymorphisms in NLRP3-Q750K (rs35829419), NLRP3 (rs10733113), CARD8-C10X (rs2043211), NLRP1 (rs8079034), and NLRP1 (rs878329).Results: Significant associations were found with the genotype AA (vs AT+TT) of rs2043211 for PsA patients compared with controls [odds ratio (OR), 95% confidence interval (CI) 1.32 (1.05-1.65), p = 0.016]; and between the C-allele of rs878329 and axial involvement of PsA [OR (95% CI) 1.37 (1.02-1.84), p = 0.035], the T-allele of rs8079034 with prescription of conventional synthetic disease-modifying anti-rheumatic drugs [OR (95% CI) 1.76 (1.23-2.53), p = 0.0020], the G-allele of rs10733113 and patients with a skin disease with early onset [OR (95% CI) 1.58 (1.13-2.21), p = 0.007], and the C-allele of rs35829419 and a destructive/deforming disease [OR (95% CI) 1.63 (1.04-2.55), p = 0.030].Conclusions: This study is the first to show an association with a genetic polymorphism in an inflammasome-related gene, CARD8-C10X (rs2043211), in patients with PsA. Associations between different phenotypes of PsA and different polymorphisms of the inflammasome genes were also found. Our results indicate the involvement of inflammasome genes in the pathogenesis and disease expression of PsA.