SNP rs7130280 in lncRNA NONHSAT159216.1 confers susceptibility to Behçet's disease uveitis in a Chinese Han population

Abstract

Objective: Long noncoding RNA (lncRNA) plays a crucial role in the process of immune-mediated diseases. However, the defined involvement of lncRNA on Behçet's disease (BD) is not well known. The aim of this study was to investigate the effects of lncRNA-related single nucleotide polymorphisms (SNPs) on BD susceptibility in Chinese populations.

Methods: A two-stage case-control association study was conducted in a cohort of 1152 BD individuals and 1152 healthy controls. Genotyping was performed by a MassARRAY System. Quantified expression of the lncRNA-miRNA-mRNA molecular axis was detected by real-time PCR and western blot. The cell proliferation was measured by CCK-8 assay.

Results: Two-stage association analysis showed a significantly decreased frequency of A allele of SNP rs7130280 in BD patients compared with healthy controls [OR 0.72 (95% CI 0.64, 0.81), Pc = 1.15 × 10-6]. Functionally, SNP rs7130280 could influence the secondary structure and relative expression of NONHSAT159216.1 in human THP-1/U937 macrophages and in peripheral blood mononuclear cells from healthy volunteers. In vitro, overexpression of the rs7130280 A allele also suppressed cell proliferation. Mechanistically, rs7130280 A allele could inhibit the expression of miR-6778-5p, thus enhancing its downstream molecular RPS6KA4/IL10 in a competing endogenous RNA sponge manner.

Conclusion: Our findings suggest that NONHSAT159216.1 rs7130280 G>A might be associated with a low risk of BD and participates in a potential lncRNA-miRNA-mRNA regulatory network.

Keywords: Behçet’s disease; long noncoding RNA; miRNA; molecular genetics; polymorphism.