1. Academic Validation
  2. SNP rs7130280 in lncRNA NONHSAT159216.1 confers susceptibility to Behcet's disease in a Chinese Han population

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

  • Rheumatology (Oxford). 2022 Apr 13;keac230. doi: 10.1093/rheumatology/keac230.
Jun Zhang 1 Jian Qi 1 Jia Shu 1 Guannan Su 1 Qingfeng Cao 1 Chunjiang Zhou 1 Yao Wang 1 Peizeng Yang 1
Affiliations

Affiliation

  • 1 The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Lab of Ophthalmology, Chongqing Eye Institute, Chongqing Branch of National Clinical Research Center for Ocular Diseases, Chongqing, P. R. China.
Abstract

Objective: Long noncoding RNAs (lncRNA) play a crucial role in the process of immune-mediated diseases. However, the defined involvement of lncRNA on Behcet'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 MassARRAY System. Quantified expression of lncRNA-miRNA-mRNA molecular axis were 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 × 1 0 -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 enhanced its downstream molecular RPS6KA4/IL10 in a ceRNA Sponge manner.

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

Keywords

Behcet’s disease; long noncoding RNA; miRNA; molecular genetics; polymorphism.

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