Evaluation of Pre-miRNA-146a rs2910164 Variations and sCD40 Ligand in Egyptian Patients with Rheumatoid Arthritis

Abstract
Background: Patients with Rheumatoid Arthritis (RA) are at greater risk of developing Cardiovascular (CV) events with higher rate of subsequent mortality. MicroRNAs (miR-NAs) such as MiR-146a are thought to have an important role in the pathogenesis of RA. CD40-CD40L interaction is poten-tially involved in atherogenesis and plaque rupture in RA, it can be a risk factor in development of accelerated vascular complications in RA patients. Aim of Work: Our aim is to evaluate the level of sCD40L, investigate the genetic variations (polymorphisms) in pre-miRNA-146a rs2910164 in a cohort of Egyptian RA patients and detect their possible relation to CV risk in RA. Methods: 108 RA patients were enrolled in our study and were divided into 2 groups according to presence and absence of CV risk along with 49 controls. Genotyping of pre-microRNA-146a rs2910164 polymorphism was done by Taq-Man real-time PCR and serum sCD40L levels were measured using human soluble CD40L ELISA assay. Results: sCD40L concentration was significantly lower in RA patients without CV risk and RA patients with CV risk when compared to control group (p < 0.001), but there was no statistically significant difference when comparing both patients' groups (p=0.5). The genotype and allele frequencies of pre-microRNA-146a rs2910164 did not show a statistically significant difference between the studied groups. When comparing RA group without CV risk, RA group with CV risk and control group, GG genotype was 41.8%, 39.6% and 32.7%, GC was 40%, 49.1% and 51% and CC was 18.2%, 11.3% and 16.3%, respectively. G allele frequency in RA without CV risk group, RA with CV risk group and control group was 35.2%, 35.2% and 29.5% and C allele frequency was 34.7%, 31.4% and 33.9%, respectively. Conclusion: Pre-miRNA-146a rs2910164 gene variations were not associated with RA and does not increase the sus-ceptibility to cardiovascular disease. Low serum levels of sCD40L were detected in RA patients irrespective of the presence of cardiovascular risk. Evaluating sCD40L in patients not receiving any treatment and comparing them with post-treatment levels is recommended.