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

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.

Diagnostic role of lncRNA GAS5 and its genetic polymorphisms rs2067079, rs6790 and rs17359906 in rheumatoid arthritis

“…rs6790 was associated with the risk of RA in the recessive model. Wu et al (34) reported that the genotype frequencies of the rs6790 SNP of lncRNA GAS5 gene was significantly associated with the risk of RA, but they did not reveal the relation of this SNP with RA risk with dominant and recessive patterns. Thus, further studies are required to explain the specific role of lncRNA GAS5 and its polymorphisms in RA development.…”

Association of LncRNA‐GAS5 gene polymorphisms and PBMC LncRNA‐GAS5 level with risk of systemic lupus erythematosus in Chinese population

“…For several years, LncRNA‐GAS5 was regarded as a tumour suppressor gene. However, recent studies have shown that LncRNA‐GAS5 plays a role in the pathogenesis of immune‐mediated inflammatory diseases, such as SLE, multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease and immune thrombocytopenia 16,37‐40 . To date, there are no reports indicating an association between LncRNA‐GAS5 gene polymorphism and the risk for SLE.…”

Epigenetic alterations in Sjögren's syndrome patient saliva

“…Previous studies have linked this lncRNA to other inflammatory and autoimmune conditions [21–24]. For instance, increased H19 levels were observed in synovial tissue from rheumatoid arthritis and knee cartilage from osteoarthritis patients compared to controls, as well as muscle biopsies from inclusion body and anti‐Jo‐1‐associated myositis patients compared to controls [21–23]. Proposed mechanisms include regulation of H19 expression by stress and inflammatory signals, while H19 in turn regulates expression of a number of downstream targets via little‐understood mechanisms.…”

“…Recently, it has been proposed that lncRNAs may serve as competing endogenous RNAs capable of blocking and inhibiting micro-RNAs via complementary base pairing [20]. Previous studies have linked this lncRNA to other inflammatory and autoimmune conditions [21][22][23][24]. For instance, increased H19 levels were observed in synovial tissue from rheumatoid arthritis and knee cartilage from osteoarthritis patients compared to controls, as well as muscle biopsies from inclusion body and anti-Jo-1-associated myositis patients compared to controls [21][22][23].…”