Genetic polymorphisms of dsRNA ligating pattern recognition receptors TLR3, MDA5, and RIG-I. Association with systemic lupus erythematosus and clinical phenotypes
Genetic polymorphisms of dsRNA ligating pattern recognition receptors TLR3, MDA5, and RIG-I. Association with systemic lupus erythematosus and clinical phenotypes
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DOI：
10.1007/s00296-014-3012-4
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发表时间：
2014-10-01
影响因子：
4
通讯作者：
Jacobsen, S.
中科院分区：
文献类型：
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作者：
Enevold, C.;Kjaer, L.;Jacobsen, S.
本研究旨在证明 Toll 样受体 3、解旋酶 C 结构域 1 (IFIH1) 诱导的干扰素和 DEAD (Asp-Glu-Ala-Asp) 盒多肽 58 与系统性红斑狼疮 (SLE) 之间可能存在的关联，包括狼疮性肾炎和颧骨皮疹的表型，以及针对含核酸复合物的自身抗体的存在。在丹麦的两个队列 [哥本哈根 (CPH) 和欧登塞 (ODE)] 总共 344 名患者中进行了基因分型，并与 641 名之前进行基因分型的健康对照进行了比较。在 ODE 队列中，仅对患者进行了 IFIH1 rs1990760 多态性的基因分型。单核苷酸多态性 (SNP) 通过多重微珠测定（CPH 队列）或实时 PCR（ODE 队列）进行测定。使用 Cochran-Armitage 趋势检验对关联进行了调查。次要等位基因纯合子与主要等位基因纯合子的比值比 (OR) 表明 IFIH1 rs1990760 SNP 对 ODE 队列中的 SLE 具有保护作用 [OR 0.52，95 % 置信区间 (95 % CI) 0.31-0.88，Pcorr。 = 0.05]，但在 CPH 队列中则不然，尽管 OR 表明存在相同方向的趋势，并且当合并两个患者队列时，OR 为 0.57，95% CI 0.37-0.88。其他研究的多态性均未显示与 SLE 存在任何关联。关于表型，我们发现 CPH 队列中 rs1990760 与颧骨皮疹之间存在统计学上显着的关联，OR 表明存在保护作用（杂合子 OR 0.28，95 % CI 0.13-0.62，纯合子 OR 0.11，95 % CI 0.03-0.41，Pcorr. = 0.0001）。 rs1990760 与抗 dsDNA、抗 U1RNP 或抗 Smith 抗体之间没有显着关联。我们的研究支持了先前关于 IFIH1 rs1990760 多态性与 SLE 之间关联的发现，并表明该 SNP 也可能与 SLE 患者的颧骨皮疹相关，尽管这一发现需要证实。
This study aimed to demonstrate possible associations between genetic polymorphisms in Toll-like receptor 3, interferon induced with helicase C domain 1 (IFIH1) and DEAD (Asp-Glu-Ala-Asp) box polypeptide 58 and systemic lupus erythematosus (SLE), including the phenotypes lupus nephritis and malar rash, as well as the presence of autoantibodies against nucleic acid-containing complexes. Genotyping was carried out in two Danish cohorts [Copenhagen (CPH) and Odense (ODE)] totaling 344 patients and was compared with 641 previously genotyped healthy controls. In the ODE cohort, the patients were only genotyped for the rs1990760 polymorphism of IFIH1. Single nucleotide polymorphisms (SNPs) were determined by a multiplex bead-based assay (CPH cohort) or real-time PCR (ODE cohort). Associations were investigated using the Cochran-Armitage trend test. The odds ratio (OR) for minor allele homozygotes versus major allele homozygotes suggested a protective effect of the IFIH1 rs1990760 SNP for SLE in the ODE cohort [OR 0.52, 95 % confidence intervals (95 % CI) 0.31-0.88, Pcorr. = 0.05] but not in the CPH cohort, although the OR suggested a trend in the same direction, and when combining the two patient cohorts, ORs were 0.57, 95 % CI 0.37-0.88. None of the other investigated polymorphisms showed any association with SLE. Regarding phenotypes, we found a statistically significant association between rs1990760 and malar rash in the CPH cohort, with ORs suggesting a protective effect (OR 0.28, 95 % CI 0.13-0.62 for heterozygotes and OR 0.11, 95 % CI 0.03-0.41 for homozygotes, Pcorr. = 0.0001). There were no significant associations between rs1990760 and presence of anti-dsDNA, anti-U1RNP, or anti-Smith antibodies. Our study supports previous findings of an association between the rs1990760 polymorphism of IFIH1 and SLE and indicates that this SNP may also be associated with malar rash in SLE patients although this finding needs confirmation.