Genetic variant in microRNA-146a gene is associated with risk of rheumatoid arthritis

Abstract

Objective To investigated the association between single nucleotide polymorphisms (SNPs) in microRNA-146a ( miR-146a ) gene and susceptibility of rheumatoid arthritis (RA). Methods We systemically extracted the genetic data of miR-146a from previous genome-wide association studies (GWASs) of RA. Subsequently, we performed a replication study in an independent Chinese cohort for selected variant. A meta-analysis combined the previous GWASs with the replication study was also conducted. The epigenetic annotation and cytokine assay were used for exploring potential variant function. Results The extracted genetic association data from three previous GWASs showed that the allele T of functional SNP rs2431697 increased RA susceptibility. The significant association for the SNP was also found in the Chinese replication cohort (OR = 1.24, 95% CI = 1.06–1.46, p = 8.69E-03). The estimated effect size for this SNP was larger in Asian population than that in European population (Asian meta-analysis: OR = 1.15, 95% CI = 1.09–1.22, p = 4.37E-07; Tran-ethnic meta-analysis: OR = 1.07, 95% CI = 1.04–1.10, p = 1.79E-06). The cytokine assay also showed that the risk allele T of the SNP rs2431697 is inversely associated with plasma TNF-α levels in health controls ( p = .016). Conclusions In summary, this study supports that genetic variant in miR-146a gene is associated with RA risk. KEY MESSAGES The association between SNPs in miR-146a gene and susceptibility of RA was unclear. We investigated the genetic association using GWASs data and a replication study. The SNP rs2431697 in miR-146a gene is associated with RA risk.

MicroRNA 146a is associated with diabetic complications in type 1 diabetic patients from the EURODIAB PCS

“…Therefore, serum miR-146a-5p level may be a circulating marker of the efficacy of the anti-inflammatory response and thus of the susceptibility to develop complications. Consistent with this, miR-146a-5p is a well-established marker of inflammation and is associated with a variety of immune and non-immune inflammatory conditions [ 14 , 43 – 45 ], including CVD, Alzheimer’s disease, and type 2 diabetes [ 34 , 46 – 49 ].…”

Circulating microRNAs in Hidradenitis Suppurativa

“…The expression of miR-146a-5p is changed in diabetic organs, and miR-146a-5p deficits have been involved in their pathogenesis [ 27 ]. In addition, miR-146a-5p is an accepted marker of inflammation and is related to immune and non-immune inflammatory disorders [ 25 ], as well as diseases such as Alzheimer’s, CVD, and type 2 diabetes [ 28 , 29 ].…”

CD4+T cell subset imbalances in rheumatoid arthritis

“…These cells have been termed Th1-like Th17 cells in the literature, coproduce IL-17 and IFNγ, and are known to contribute to inflammation in the context of autoimmunity [33][34][35]. Interestingly, IFNγ production in Th1-like Th17 cells has been shown to be repressed by miR-146a [35] and loss of function polymorphisms in the microRNA-146a (miR-146a) gene have been associated with an increased risk of developing RA and lupus in both European and Asian genetic association studies [36,37]; taken together, these data provide some mechanistic evidence that Th1-like Th17 cells are involved in the pathogenesis of RA. The methods outlined in this paper easily detect an increase of this subset in RA.…”