Association of microRNA 17 host gene variant (rs4284505) with susceptibility and severity of systemic lupus erythematosus

Abstract

Objective MicroRNAs are large family clusters of small noncoding RNAs that implicated in genetic and epigenetic regulation of several immunological processes and pathways. As an epigenetic modifier, the microRNA 17‐92 cluster host gene (MIR17HG) has been shown to regulate the expression of genes involved in systemic lupus erythematosus (SLE) pathway. This study aimed to explore the association of MIR17HG (rs4284505; A>G) variant with SLE development and phenotype in a sample of the Eastern Mediterranean population. Methods A total of 326 participants (163 patients with SLE and 163 healthy controls) were enrolled in this study. The different genotypes of the MIR17HG (rs4284505) variant were characterized using the TaqMan real‐time polymerase chain reaction technique. Association with the available clinical and laboratory data, including the systemic lupus erythematosus disease activity index (SLEDAI), was also executed. Results The MIR17HG (rs4284505) variant showed a protective effect against developing SLE under heterozygote (A/G vs A/A; odds ratio [OR] = 0.10, 95% confidence interval [CI] = 0.05‐0.20, P < 0.001) and dominant (A/G+G/G vs A/A; OR = 0.39, 95% CI = 0.25‐0.61, P < .001) models. This association was consistent even after SLE stratified by lupus nephritis. In contrast, rs4284505 (G/G) genotype conferred increased susceptibility to SLE (G/G vs A/A+A/G; OR = 2.15, 95% CI = 1.31‐3.53, P = .002). Moreover, the rs4284505 variant showed a statistically significant association with mucocutaneous lesions and SLEDAI scores (all P < .05). Conclusion This study is the first one to explore that the MIR17HG rs4284505 is associated with SLE risk; (A/G) genotype conferred a protective effect, while the (G/G) genotype showed increased susceptibility to SLE and association with the disease severity in the study population.

Association of microRNA-34a rs2666433 (A/G) Variant with Systemic Lupus Erythematosus in Female Patients: A Case-Control Study

“…The microRNA family of non-coding RNAs has been implicated in immune system homeostasis, and its genetic variants and gene signature deregulation are associated with several immunological disorders, including SLE [ 32 , 39 , 40 , 41 , 42 ]. The present study identified for the first time that MIR34A rs2666433 A/A and A/G genotypes are less likely to develop SLE in the study population.…”

“…MiR-34a target genes code for different histone family members (i.e., H2A, H2B, H3, and H4) that are implicated in tolerance mechanism/autoantigen clearance and the “major histocompatibility complex class II (MHCII)”, which plays an essential role in antigen presentation [ 31 ]. All the stages of antigen processing and autoantibodies generation lead to tissue injury and end-organ damage (left panel) [ 32 ]. More detail for gene names and functions are provided in Table S1 .…”

MicroRNA-17-92a-1 Host Gene (MIR17HG) Expression Signature and rs4284505 Variant Association with Alopecia Areata: A Case–Control Study

“…The applied protocol was run blindly to the case/control status with a final volume of 20 μL containing the extracted genomic DNA (20 ng), TaqMan SNP Genotyping Assay Mix (1 μL) (assays ID: C__26557482_10, Applied Biosystems), and TaqMan Universal PCR Master Mix (10 μL) (Catalog no. 4371353) [ 17 ]. Two-allele-specific TaqMan minor groove-binding (MGB) probes containing distinct fluorescent dyes were included in the genotyping assay.…”

“…A common variant (rs4284505) exists within the MIR17HG gene with a minor allele frequency (MAF) of 0.5. It was previously cited to be in linkage disequilibrium with an upstream polymorphism related to multiple sclerosis [ 16 ] and to be associated with systemic lupus erythematosus (SLE) [ 17 ]. The impact of this polymorphism on AA susceptibility and phenotype has not been studied before, especially in the present population.…”

MIR17HG polymorphisms contribute to high-altitude pulmonary edema susceptibility in the Chinese population

“…These findings indicate that MIR17HG plays an important role in lung diseases. A number of studies have shown that MIR17HG polymorphisms are associated with various disease risks 15 , and multiple reports have shown that gene polymorphisms are associated with HAPE risk 16 . However, there is no report on the relationship between MIR17HG polymorphisms and HAPE risk..…”