Decreased H19, GAS5, and linc0597 Expression and Association Analysis of Related Gene Polymorphisms in Rheumatoid Arthritis

Jun Wu,Rui-Xue Leng,Dong-Qing Ye,Yu-Lan Zhao,Bao-Zhu Li,Hai-Feng Pan,Tian-Ping Zhang

doi:10.3390/biom10010055

Abstract

Long noncoding RNAs (lncRNAs) widely participate in human diseases by regulating gene transcription, modulating protein function, or acting as ceRNAs. Yet, their roles in rheumatoid arthritis (RA) remain obscure. In this study, the expression of three lncRNAs (H19, GAS5, and linc0597) in peripheral blood mononuclear cells (PBMCs) were detected in 77 RA patients and 78 controls using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). The association of lncRNAs related gene polymorphisms with RA were evaluated in 828 RA patients and 780 controls using TaqMan single nucleotide polymorphism (SNP) genotyping assays. We observed that the expression levels of H19, GAS5 and linc0597 were down-regulated in PBMCs of RA patients, of which GAS5 level decreased in patients with hypocomplementemia, and negatively correlated with C-reactive protein (CRP) level in RA patients. Moreover, we highlighted two related potential functional SNPs, GAS5 rs6790 and linc0597 rs2680700 for associations with RA susceptibility. The precise roles of these lncRNAs in mechanism of RA remain to be further explored.

Highlights

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by autoantibodies, systemic inflammation, persistent synovitis, and irreversible joint cartilage and bone destruction [1].Some extra-articular symptoms, such as pleuritis and rheumatoid vasculitis, can cause complications and poor prognosis of RA [1]
We aimed to investigate the three Long noncoding RNAs (lncRNAs) expression levels in peripheral blood mononuclear cells (PBMCs) of RA patients, as well as explore the associations of lncRNAs expression and their gene single nucleotide polymorphisms (SNPs) with RA susceptibility
During the years 2016–2017, RA patients and controls were enrolled to investigate the expression of H19, GAS5 and linc0597 in PBMCs, 828 RA patients and 780 controls were recruited to explore the association of gene polymorphisms with disease susceptibility

Summary

Introduction

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by autoantibodies, systemic inflammation, persistent synovitis, and irreversible joint cartilage and bone destruction [1]. Some extra-articular symptoms, such as pleuritis and rheumatoid vasculitis, can cause complications and poor prognosis of RA [1]. RA affects approximately 1% of the global population [2]. Clinical trials and epidemiological data have indicated that the interaction of environmental factors, genetic factors, autoimmunity, endocrine system, and infection contributes to the initiation and progression of RA [1,3,4]. Abundant genetic variants were broadly confirmed to play major roles in RA [1]. Emerging evidence has revealed that a subset of noncoding RNAs (ncRNAs) play pivotal roles in RA [7]

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