PDF(Pubmed)
Abstract：
The melanoma differentiation-associated protein 5 (MDA5; encoded by the IFIH1 gene) mediates the activation of the interferon pathway in response to a viral infection. This protein is also upregulated in autoimmune diseases and psoriasis skin lesions. IFIH1 gene variants that increase MDA5 activity have been associated with an increased risk for immune-mediated diseases, including psoriasis. Our aim is to determine the association between three IFIH1 variants (rs35337543 G/C, intron8 + 1; rs35744605 C/A, Glu627Stop; and rs1990760 C/T, Ala946Thr) and the main clinical findings in a cohort of Spanish patients with psoriasis (N = 572; 77% early-onset). Early-onset psoriasis patients (EOPs) had a significantly higher frequency of severe disease and the Cw6*0602 allele. Carriers of rs1990760 T (946Thr) were more common in the EOPs (p < 0.001), and the effect was more pronounced among Cw6*0602-negatives. This variant was also associated with an increased risk of psoriatic arthritis (PsA) independent from other factors (OR = 1.62, 95%CI = 1.11-2.37). The rs3533754 and rs35744605 polymorphisms did not show significant differences between the two onset age or PsA groups. Compared to the controls, the 946Thr variant was more common in the EOPs (nonsignificant difference) and significantly less common in patients aged >40 years (p = 0.005). In conclusion, the common IFIH1 rs1990760 T allele was significantly more frequent in early-onset compared to late-onset patients. This variant was also an independent risk factor for PsA in our cohort. Our study reinforces the widely reported role of the IFIH1 gene variants on psoriatic disease.
摘要：
黑色素瘤分化相关蛋白5（MDA5；由IFIH1基因编码）介导干扰素途径的激活，以响应病毒感染。这种蛋白质在自身免疫性疾病和牛皮癣皮肤病变中也被上调。增加MDA5活性的IFIH1基因变异与免疫介导疾病的风险增加有关。包括牛皮癣。我们的目的是确定三个IFIH1变体(rs35337543G/C，intron8+1;rs35744605C/A,Glu627Stop;和rs1990760C/T,Ala946Thr）和西班牙银屑病患者队列中的主要临床发现（N=572；77％的早发性）。早发性银屑病患者（EOP）的严重疾病和Cw6*0602等位基因的频率明显更高。rs1990760T(946Thr)的载体在EOP中更常见(p<0.001)，在Cw6*0602阴性者中效果更为明显。这种变异也与银屑病关节炎（PsA）的风险增加相关，而与其他因素无关（OR=1.62，95CI=1.11-2.37）。rs3533754和rs35744605多态性在两个发病年龄或PsA组之间没有显着差异。与对照相比，946Thr变异体在EOP中更为常见(无显著性差异),而在年龄>40岁的患者中更为少见(p=0.005).总之,与晚发型患者相比,常见IFIH1rs1990760T等位基因在早发型患者中明显更常见.该变异也是我们队列中PsA的独立危险因素。我们的研究加强了广泛报道的IFIH1基因变体在银屑病疾病中的作用。
