miRNA-499 Gene Polymorphism Tied to Autoimmune Disease Risk, Analysis Shows

The study found associations between miRNA-499 polymorphism and autoimmune disease risk in Caucasian and Asian populations, including a significantly increased risk of rheumatoid arthritis and systemic lupus erythematosus.

A new meta-analysis shows a significant correlation between the micro RNA-499 rs3746444 polymorphism and the risk of autoimmune diseases, providing new clarity surrounding an association that had previously been identified in smaller studies.

The report was published in the journal PLOS One.

Corresponding author Baoxin Ma, PhD, of the Central Affiliated Hospital of Shandong First Medical University, in China, and colleagues, explained that micro RNAs (miRNAs) regulate the expressions of their target genes, as well as physiological and pathological processes, due to their presence in many biological fluids. They have been identified as biomarkers for a number of diseases, including autoimmune diseases.

MiRNA-499 rs3746444, in particular, has been linked with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Graves’ disease, and ankylosing spondylitis, Ma and colleagues said, but the data underlying the associations is controversial. While a number of meta-analyses have been performed examining links between miRNA polymorphism and autoimmune diseases, the authors said most of those have been focused narrowly on 1 or 2 autoimmune diseases, thus a need exists for a more comprehensive examination of the issue.

The investigators searched for studies that evaluated the association between miRNA-499 polymorphism and autoimmune diseases and had available and sufficient data, including the genotype frequency in both case and control groups. They excluded review papers, studies without controls, and studies in which insufficient data were available to calculate odds ratios and confidence intervals.

From an initial pool of 244 studies, the authors identified 17 that met their inclusion criteria. Eight of the studies were focused on Asian populations, and the remaining 9 focused on Caucasian populations. In total, 4376 cases and 4991 controls were used in the studies.

Overall, the pooled analysis suggested a significant association between miRNA-499 gene polymorphism and autoimmune diseases (T vs. C: OR = 0.877; 95% CI, 0.774-0.993; P = .039). The link was confirmed in both Caucasian (TT vs. TC+CC: OR = 0.779; 95% CI, 0.622-0.976; P = .030) and Asian (T vs. C: OR = 0.895; 95% CI, 0.808-0.992; P = .035) populations.

The meta-analysis also found an association between the polymorphism and Behcet’s disease, RA, SLE, and ulcerative colitis. The authors said previous genome-wide assessment studies did not find similar links; however, they said genome-wide assessment studies tend to be skewed more toward European populations and do not identify all genetic determinants of complex traits. They said further study will be needed to fully understand the disparity between this meta-analysis and those earlier studies.

Ma and colleagues said their study was limited by the small number of studies available for certain disease types, and the range of populations and environments included. They said environmental factors might have influenced the results, but they did not have the ability to assess gene-environment interactions.

Still, the investigators said the size of their meta-analysis is significantly larger than earlier analyses, and they noted that 7 studies in the analysis pertained to RA, giving them confidence in that association, in particular.


Kong X, Diao S, Xu H, Sun J, Ma B. Association between miRNA-499 gene polymorphism and autoimmune diseases: a meta-analysis. PLoS One. 2022;17(3):e0266265. doi:10.1371/journal.pone.0266265

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