Dataset Information

Association between genetic variants of microRNA-21 and microRNA-155 and systemic lupus erythematosus: A case-control study from a Chinese population.

ABSTRACT:

Background

Systemic lupus erythematosus (SLE) is a common autoimmune disease, and its pathogenesis remains unclear. The alteration of genetic materials is believed to play a role in SLE development. This study evaluated the association between the genetic variants of microRNA-21 (miR-21) and microRNA-155 (miR-155) and SLE.

Methods

The SNaPshot genotyping method was used to detect the genotypes of selected SNPs in patients and controls. The expression of miR-21 and miR-155 was analyzed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The functional annotation and the biological effects of SNPs were assessed by HaploReg V4.1 and Regulome DB V2.0 software. The Hardy-Weinberg equilibrium test was used to gather statistics, and odds ratios (ORs) and 95% confidence intervals (CIs) were evaluated by logistic regression.

Results

The distribution difference of TA genotype in rs767649 was observed (TA vs. T/T: OR = 0.68, 95%CI, 0.48-0.95, p = 0.026). There was a significant difference in the T/A + A/A (T/A + A/A vs. T/T: OR = 0.68, 95%CI, 0.49-0.94, p = 0.020). A significant difference in T allele distribution was found in the depressed complement of SLE (T vs. A: OR = 0.67, 95%CI, 0.47-0.95, p = 0.026). There were significant differences in genetic variants of rs13137 between the positive and the negative SSB antibodies (Anti-SSB) (T vs. A: OR = 0.67, 95%CI, 0.47-0.95, p = 0.026; T/A + T/T vs. AA: OR = 2.23, 1.18-4.49, p = 0.013). The expression levels of miR-21 and miR-155 were significantly higher in patients than in controls (p < 0.001).

Conclusions

This study provides novel insight that genetic variants of rs767649 and rs13137 are associated with susceptibility to SLE.

SUBMITTER: Wang R

PROVIDER: S-EPMC9279951 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveTo evaluate the specificity of expression patterns of cell-free circulating microRNAs (miRNAs) in systemic lupus erythematosus (SLE).MethodsTotal RNA was purified from plasma, and 45 different specific, mature miRNAs were determined using quantitative reverse transcription-polymerase chain reaction assays. A total of 409 plasma samples were obtained from 364 different patients with SLE, healthy control subjects, and control subjects with other autoimmune diseases. The results in the primary cohort of 62 patients with SLE and 29 healthy control subjects were validated in 2 independent cohorts: a validation cohort comprising 68 patients with SLE and 68 healthy control subjects, and a disease control cohort comprising 20 patients with SLE (19 of whom were from the other validation cohort), 46 healthy control subjects, 38 patients with vasculitis, 18 patients with rheumatoid arthritis, and 20 immunosuppressed patients.ResultsSeven miRNAs were statistically significantly differentially expressed in plasma from patients with SLE. The expression of miRNA-142-3p (miR-142-3p) and miR-181a was increased, and the expression of miR-106a, miR-17, miR-20a, miR-203, and miR-92a was decreased. In addition, the expression of miR-342-3p, miR-223, and miR-20a was significantly decreased in SLE patients with active nephritis. A predictive model for SLE based on 2 or 4 miRNAs differentiated patients with SLE from control subjects (76% accuracy) when validated independently (P < 2 × 10(-9) ). Use of the 4-miRNA model provided highly significant differentiation between the SLE group and disease controls, except for those with vasculitis.ConclusionCirculating miRNAs are systematically altered in SLE. A 4-miRNA signature was diagnostic of SLE, and a specific subset of miRNA profiles was associated with nephritis. All of the signature miRNAs target genes in the transforming growth factor β signaling pathways. Other targets include regulation of apoptosis, cytokine-cytokine receptors, T cell development, and cytoskeletal organization. These findings highlight possible dysregulated pathways in SLE and suggest that circulating miRNA patterns distinguish SLE from other immunoinflammatory phenotypes.