MIR149 rs2292832 and MIR499 rs3746444 Genetic Variants Associated with the Risk of Rheumatoid Arthritis

Abstract

Introduction: MicroRNAs (miRNAs) are small non-coding RNAs that play a key role in post-transcriptional modulation of individual genes’ expression. Several miRNA variants from different populations are known to be associated with an increased risk of rheumatoid arthritis (RA). Aim: This study was undertaken with the aim to investigate the association of single nucleotide variants; namely, rs2292832, rs3746444, rs11614913, rs1044165, and rs767649 of MIR149, MIR499, MIR196, MIR223, and MIR155, respectively, with RA in the Pakistani population. Methods: A case-control study was performed by recruiting and genotyping a total of 600 individuals (300 cases and 300 controls) for these five variants using a TaqMan single-nucleotide polymorphism (SNP) genotyping assay. The resultant genotypic data was statistically analyzed through a chi-squared test for its association with RA under different inheritance models. Results: We found a significant association of rs2292832 with RA at genotypic (co-dominant (p < 0.0001), dominant (CC vs. TT + CT: OR 2.063 (1.437–2.962); p = 0.0001), recessive (TT vs. CT + CC: OR 0.376 (0.259–0.548); p < 0.0001)), and allelic (allele C) levels ((OR 0.506 (0.402–0637); p < 0.0001)). Similarly, the rs3746444 showed a significant association with RA under co-dominant (p = 0.0001), dominant (GG vs. AA + AG: OR 5.246 (3.414–8.061); p < 0.0001), recessive (AA vs. GG + AG: OR 0.653 (0.466–0.916); p = 0.014), and additive models (G vs. A; OR 0.779 (0.620–0.978); p = 0.03). However, we did not observe any significant association of rs11614913, rs1044165, or rs767649 with RA in our subjects. Conclusion: To our knowledge, this was the first study that investigated and found an association between functional polymorphisms in miRNAs and RA in the Pakistani population.