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Updated: Nov 3, 2025

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
Genetic variant in microRNA-146a gene is associated with risk of rheumatoid arthritis
Lin-Lin Zhang1,2, Xiao-Xiao Wu1,2, Xu-Fan Wang1,2
1Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, PR China.
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 MESSAGESThe 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.
Insights
Single nucleotide polymorphisms (SNPs) in the microRNA-146a (miR-146a) gene are associated with rheumatoid arthritis (RA) risk. The study identified a specific SNP, rs2431697, as increasing susceptibility to RA, particularly in Asian populations.
Area of Science:
- Genetics
- Immunology
- Molecular Biology
Background:
- Rheumatoid arthritis (RA) is a chronic autoimmune disease with a complex genetic component.
- MicroRNA-146a (miR-146a) plays a role in immune regulation and has been implicated in various inflammatory conditions.
- The association between specific single nucleotide polymorphisms (SNPs) in the miR-146a gene and RA susceptibility requires further investigation.
Purpose of the Study:
- To investigate the association between SNPs in the miR-146a gene and the susceptibility to rheumatoid arthritis (RA).
- To identify specific miR-146a variants that may influence RA risk.
- To explore the functional implications of identified variants in relation to RA pathogenesis.
Main Methods:
- Systematic extraction of genetic data for miR-146a from existing genome-wide association studies (GWASs) on RA.
- Conducting a replication study in an independent Chinese cohort to validate findings for selected variants.
- Performing a meta-analysis combining GWAS data with the replication study results.
- Utilizing epigenetic annotation and cytokine assays to explore potential variant functions.
Main Results:
- Genetic association data from three GWASs indicated that the T allele of the functional SNP rs2431697 increases RA susceptibility.
- The association of SNP rs2431697 with RA was confirmed in the Chinese replication cohort (OR = 1.24, 95% CI = 1.06-1.46, p = 8.69E-03).
- The effect size of rs2431697 was larger in Asian populations compared to European populations (Asian meta-analysis: OR = 1.15, 95% CI = 1.09-1.22, p = 4.37E-07).
- The risk allele T of rs2431697 was inversely associated with plasma TNF-α levels in healthy controls (p = 0.016).
Conclusions:
- Genetic variants within the miR-146a gene are associated with an increased risk of rheumatoid arthritis.
- The SNP rs2431697 in the miR-146a gene is a significant risk factor for RA susceptibility.
- These findings contribute to understanding the genetic underpinnings of RA and highlight miR-146a as a potential player in its pathogenesis.
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