Paradowska-Gorycka Agnieszka, Wajda Anna, Stypinska Barbara, Walczuk Ewa, Walczyk Marcela, Felis-Giemza Anna, Poluch Aleksandra, Olesińska Marzena
Department of Molecular Biology, National Institute of Geriatrics, Rheumatology and Rehabilitation, 02-637 Warsaw, Poland.
Department of Connective Tissue Diseases, National Institute of Geriatrics, Rheumatology and Rehabilitation, 02-637 Warsaw, Poland.
J Clin Med. 2019 Nov 21;8(12):2046. doi: 10.3390/jcm8122046.
Mixed connective tissue disease (MCTD) is a rare complex autoimmune disease in which autoantigens are recognized by endosomal TLRs. Their activation induces a higher secretion of the type I interferons, IFN-γ and the up-regulation of the INF-inducible genes. The present study aimed to investigate whether SNPs that are located in the IFN-A, IFN-B, and IFN-G genes are associated with MCTD. 145 MCTD patients and 281 healthy subjects were examined for IFN-A, IFN-B, and IFN-G genetic variants by TaqMan SNP genotyping assay. ELISA determined IFN-α/-β/-γ serum levels. Among the seven tested SNPs, four polymorphisms: IFN-A rs10757212, IFN-A rs3758236, IFN-G rs2069705, IFN-G rs2069718, as well as INF-G rs1861493A/rs2069705A/rs2069718G haplotype were significantly associated with a predisposition for MCTD. Raynaud's phenomenon, erosive arthritis, swollen hands and fingers, and sclerodactyly were significantly more frequently observed in MCTD patients with IFN-G rs2069718 G allele than in patients with IFN-G rs2069718 A allele. We also found that anti-U1-A autoantibodies most frequently occurred in MCTD patients with rs2069718 GA genotype, while the IFN-G rs2069705 AG and rs2069718 GA genotypes might be a marker of anti-Ro60 presence in MCTD patients. Our results indicate that IFN-G genetic variants may be potential genetic biomarkers for MCTD susceptibility and severity.
混合性结缔组织病（MCTD）是一种罕见的复杂自身免疫性疾病，其中自身抗原由内体Toll样受体（TLRs）识别。它们的激活诱导I型干扰素、IFN-γ的更高分泌以及INF诱导基因的上调。本研究旨在调查位于IFN-A、IFN-B和IFN-G基因中的单核苷酸多态性（SNPs）是否与MCTD相关。通过TaqMan SNP基因分型测定法对145例MCTD患者和281名健康受试者进行了IFN-A、IFN-B和IFN-G基因变异检测。酶联免疫吸附测定（ELISA）测定IFN-α/-β/-γ血清水平。在七个检测的SNPs中，四个多态性：IFN-A rs10757212、IFN-A rs3758236、IFN-G rs2069705、IFN-G rs2069718，以及INF-G rs1861493A/rs2069705A/rs2069718G单倍型与MCTD易感性显著相关。与IFN-G rs2069718 A等位基因的患者相比，IFN-G rs2069718 G等位基因的MCTD患者中雷诺现象、侵蚀性关节炎、手部和手指肿胀以及指端硬化明显更常见。我们还发现，抗U1-A自身抗体最常出现在rs2069718 GA基因型的MCTD患者中，而IFN-G rs2069705 AG和rs2069718 GA基因型可能是MCTD患者中抗Ro60存在的标志物。我们的结果表明，IFN-G基因变异可能是MCTD易感性和严重程度的潜在遗传生物标志物。
