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

• Published in: Immunity, Inflammation and Disease Vol. 8; no. 4; pp. 595 - 604
• Main Authors: Abdel‐Gawad, Abdelhady R., Shaheen, Sameerah, Babteen, Nouf A., Toraih, Eman A., Elshazli, Rami M., Fawzy, Manal S., Gouda, Nawal S.
• Format: Journal Article
• Language: English
• Published: Bognor Regis John Wiley & Sons, Inc 01-12-2020; John Wiley and Sons Inc; Wiley
• Subjects: Age; Antibodies; Antigens; Autoimmune diseases; Automation; Blood & organ donations; Confidence intervals; Deoxyribonucleic acid; Disease; DNA; Family medical history; Genes; genetic polymorphisms; Immunology; Laboratories; Lupus; MicroRNAs; MIR17HG; Original Research; Pathogenesis; Polymerase chain reaction; Principal components analysis; Rheumatology; rs4284505; Statistical analysis; systemic lupus erythematosus; T cell receptors; Tumor necrosis factor-TNF; Suez Canal; Germany
• ISSN: 2050-4527; 2050-4527
• DOI: 10.1002/iid3.344

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.
For the first time, this study showed that the microRNA 17‐92 cluster host gene (MIR17HG) is associated with the systemic lupus erythematosus (SLE) risk. The MIR17HG (A/G) genotype conferred a protective effect, while the (G/G) genotype showed increased susceptibility to SLE and association with the disease severity in a sample of the Eastern Mediterranean population.