Juárez-Vicuña Yaneli, Pérez-Ramos Julia, Adalid-Peralta Laura, Sánchez Fausto, Martínez-Martínez Laura Aline, Ortiz-Segura María Del Carmen, Pichardo-Ontiveros Edgar, Hernández-Díazcouder Adrián, Amezcua-Guerra Luis M, Ramírez-Bello Julian, Sánchez-Muñoz Fausto
Department of Immunology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
Department of Biological Systems, Universidad Autónoma Metropolitana-Xochimilco, Mexico City, Mexico.
Front Genet. 2021 Jun 2;12:647487. doi: 10.3389/fgene.2021.647487. eCollection 2021.
Systemic lupus erythematosus (SLE) is an autoimmune disease with a complex etiology. Various genetic factors are associated with susceptibility to developing SLE and contribute to its onset and progression. Different single-nucleotide polymorphisms (SNPs) have been associated with SLE in several populations. The rs12979860 SNP in interferon lambda 3/4 (IFNλ3/4) is significantly associated with SLE susceptibility in patients negative for nephritis in Taiwanese people, and interferon-stimulated genes (ISGs) are differentially expressed in normal liver by the rs12979860 genotype. This study aimed to investigate whether rs12979860 is associated with the presence of SLE and lupus nephritis in Mexican individuals as well as with the expression of several ISGs in SLE patients. In total, 439 SLE patients and 358 healthy donors were genotyped for rs12979860 using real-time PCR, and allelic discrimination plots were constructed. Additionally, peripheral blood mononuclear cells (PBMCs) were isolated from the venous blood of SLE patients by centrifugation ( = 78). The mRNA levels of 2'-5'-oligoadenylate synthetase like (OASL), myxovirus resistance 1 (MX1), 2'5'-oligoadenylate synthetase 1 (OAS1), interferon-stimulated gene 15 (ISG15) and lymphocyte antigen 6 complex, locus E (LY6E) were determined using real-time PCR. The distributions of rs12979860 genotypes and allele frequencies were compared between SLE patients and healthy donors; case-control analysis revealed that rs12979860 was not associated with SLE susceptibility (OR 1.18, 95% CI 0.97-1.45, = 0.08) or with the risk for lupus nephritis (OR 0.913, 95% CI 0.590-1.411, = 0.682). However, OASL expression levels in PBMCs were significantly different between rs12979860 genotypes in SLE patients: median OASL mRNA levels were significantly higher in patients carrying the CC genotype (197.10, IQR 71.10-411.17) than in those with CT/TT genotypes (173.75, IQR 58.80-278.75, = 0.016). Our results suggest that the SNP rs12979860 does not play a relevant role in susceptibility to SLE in Mexican individuals. However, IFNλ3/4 genotypes appear to be associated with OASL expression in PBMCs from patients with SLE.
系统性红斑狼疮（SLE）是一种病因复杂的自身免疫性疾病。多种遗传因素与SLE的易感性相关，并促成其发病和进展。不同的单核苷酸多态性（SNP）已在多个人群中与SLE相关联。台湾人群中，干扰素λ3/4（IFNλ3/4）中的rs12979860 SNP与肾炎阴性患者的SLE易感性显著相关，且干扰素刺激基因（ISG）在正常肝脏中因rs12979860基因型而有差异表达。本研究旨在调查rs12979860是否与墨西哥个体的SLE及狼疮性肾炎的存在相关，以及是否与SLE患者中几种ISG的表达相关。总共对439例SLE患者和358名健康供体使用实时PCR对rs12979860进行基因分型，并构建等位基因鉴别图。此外，通过离心从SLE患者的静脉血中分离外周血单个核细胞（PBMC）（n = 78）。使用实时PCR测定2'-5'-寡腺苷酸合成酶样（OASL）、抗黏液病毒1（MX1）、2'5'-寡腺苷酸合成酶1（OAS1）、干扰素刺激基因15（ISG15）和淋巴细胞抗原6复合体E位点（LY6E）的mRNA水平。比较SLE患者和健康供体之间rs12979860基因型的分布和等位基因频率；病例对照分析显示，rs12979860与SLE易感性（比值比1.18，95%置信区间0.97 - 1.45，P = 0.08）或狼疮性肾炎风险（比值比0.913，95%置信区间0.590 - 1.411，P = 0.682）无关。然而，SLE患者中rs12979860基因型之间PBMC中的OASL表达水平存在显著差异：携带CC基因型的患者（197.10，四分位距71.10 - 411.17）的OASL mRNA中位数水平显著高于携带CT/TT基因型的患者（173.75，四分位距58.80 - 278.75，P = 0.016）。我们的结果表明，SNP rs12979860在墨西哥个体对SLE的易感性中不发挥相关作用。然而，IFNλ3/4基因型似乎与SLE患者PBMC中的OASL表达相关。
