: Micro ribonucleic acids (miRNAs) are noncoding RNAs, recently implicated as potential biomarkers or therapeutic targets for autoimmune diseases such as rheumatoid arthritis (RA). The aim of this study is to assess the role of miRNA Let-7 in the plasma of RA. : Trained medical staff already enrolled for the study collected blood samples from healthy controls ( = 42) and RA patients ( = 44). In the laboratory, these samples were centrifuged at 2000 rpm for 8 minutes to separate serum from the sample, which was then transferred to a plain vial. Until transport to the genetic lab, samples were stored at -20°C Deoxyribonucleic acid (DNA) was isolated using a standard protocol cohort of controls and patient blood samples. Quantification of DNA was conducted using ultraviolet (UV) spectroscopy, and DNA quality was assessed on 0.8% agarose gel. A comparison of genotype frequencies in the different study groups was performed using the Chi-squared test, while a comparison of allelic frequencies was conducted using Fisher's exact test. : Variations of alleles, such as 16539423 (G>T), 16539433 (T>G), and 16539629 (A>T) were found only in RA patients. On the other hand, 16539617 (T>A), 16539622 (G>T), and 16539624 (T>C) were found only in control cases. Five sequences (three RA variants and two control variants) with minimal alignment were compared to the wild-type sequence. We found that the sequence modification of pre-miRNA 16539623 del G was significantly higher and had a risk allele in the study group [odds ratio (OR) = 3.29]. : Rheumatoid arthritis (RA) is an autoimmune disorder that presents with a variety of clinical manifestations. Genetic factors possibly account for about 60% of disease susceptibility and expression, thus playing a very important role in disease pathogenesis. : Gauri LA, Liyakat N, Dadhich D, Role of miRNA Let-7 in Plasma of Rheumatoid Arthritis. J Assoc Physicians India 2023;71(11):50-52.

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