Interaction of miR-181b and IFNA1 Polymorphisms on the Risk of Systemic Lupus Erythematosus

Abstract

Introduction. A previous work has discovered that chromosome 1q32 locus linked to the risk of systemic lupus erythematosus (SLE) and miR-181b located on the susceptibility site with downregulation inversely correlating to its target molecular interferon alpha 1 (IFNA1). The purpose of this study was to investigate the association of miR-181b and IFNA1 polymorphisms with IS risk. Methods. The miR-181b rs322931, IFNA1 rs1332190, and rs10811543 were genotyped using a Multiplex SNaPshot assay. miR-181b expression levels in plasma of SLE patients and controls were analyzed using quantitative PCR. Results. The rs322931 CT, CT/TT, and T allele exerted an increased trend of SLE risk (CT vs. CC: adjusted OR=1.71, 95% CI 1.16-2.50, P=0.01; CT/TT vs. CC: adjusted OR=1.45, 95% CI 1.08-1.95, P=0.01; T vs. C: adjusted OR=1.38, 95% CI 1.07-1.79, P=0.01). Combined genotypes of the rs322931 CT/TT+rs1332190 TT and the rs322931 CC+rs10811543 AG/AA also revealed an increased risk of SLE. Gene-gene interaction analysis showed that a three-locus model consisting of rs322931, rs1332190, and rs10811543 attributed an increased risk of SLE. Further genotype-phenotype analysis revealed that rs322931 CT/TT carriers displayed lower levels of miR-181b. Conclusions. These findings indicate that the miR-181b rs322931 may be singly and jointly responsible for the etiology of SLE by altering miR-181b expression.

The emerging role of noncoding RNAs in systemic lupus erythematosus: new insights into the master regulators of disease pathogenesis

“…Although IFNA1 rs1332190 and rs10811543 alone were not significantly related to SLE, a combined analysis of these three factors simultaneously augmented the risk of disease progression. Therefore, He et al , 109 finding a correlation between miR-181b expression and rs322931 and mentioning a downregulation in miR-181b levels in SLE patients due to rs322931 CT /TT genotype compared with normal individuals once again noted the importance of ncRNAs in SLE. Due to the effects of SNPs and their correlation with microRNAs, the association of autophagy-related gene, MTMR3 SNP rs12537, which is the main target gene of miR-181-a, has been investigated with SLE progression.…”

The Pathogenesis, Molecular Mechanisms, and Therapeutic Potential of the Interferon Pathway in Systemic Lupus Erythematosus and Other Autoimmune Diseases

“…Within the past 13 years, genome-wide association and pathway-centered sequencing studies have identified many polymorphisms in interferon pathway genes that predispose an individual to developing SLE, including polymorphisms affecting the STAT4 , IRF3 , and IFNA1 genes [ 70 , 71 , 72 , 73 , 74 ]. While single polymorphisms may not be sufficient to cause autoimmunity alone, accumulating numbers of risk variants may cause the immune system to become overwhelmed, leading to immune dysregulation [ 24 , 75 ].…”

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

“…[13][14][15][16] Recently, some studies found that mi-croRNAs were involved in different types of autoimmune diseases, including SLE. [17][18][19][20] The miR-21 is considered a prospective marker and has been identified in many autoimmune diseases. 21 Some evidence has revealed that higher miR-21 expression can be found in lupus when compared with control groups.…”

“…Several studies have demonstrated that microRNA‐21 ( miR‐21 ) is involved in different kinds of diseases, such as cancers, diabetes, and neurological diseases 13–16 . Recently, some studies found that microRNAs were involved in different types of autoimmune diseases, including SLE 17–20 . The miR‐21 is considered a prospective marker and has been identified in many autoimmune diseases 21 .…”