The rs2910164 variant is associated with reduced miR-146a expression but not cytokine levels in patients with type 2 diabetes
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Previous reports have demonstrated that genetic variations in microRNAs regulome could affect microRNAs-mediated regulation. Therefore, in the present study we were aimed at (1) comparison of microRNA 146-a (miR-146a) peripheral blood mononuclear cells (PBMCs) and plasma levels between diabetic patients and controls, and (2) investigating the possible association of rs2910164 with miR-146a and its related target genes expression and also serum cytokine levels.
The study population consisted of 60 subjects including 30 type 2 diabetes (T2D) patients and 30 controls with determined genotypes for rs2910164. The RNA expression levels were determined by real-time PCR. Moreover, TNF-α, IL-6, IL-10 and IL-1β serum levels were measured using ELISA method.
Our results showed that the miR-146a expression levels were significantly decreased in PBMCs (P = 0.004) and plasma (P = 0.008) samples of patients with T2D compared to healthy participants. In addition, we observed that IRAK1 mRNA expression—but not TLR4, TRAF6 and NFĸB—was significantly increased in patients with T2D compared to controls (P = 0.028). The relative expression levels of miR-146a in plasma and PBMCs samples of diabetic patients with the rs2910164 GG genotypes were significantly higher than that in CC (P < 0.05). Moreover, no significant differences were found in miR-146a targets and cytokine levels between the rs2910164 different genotypes.
Our study demonstrated that miR-146a circulating levels were significantly elevated in controls compared with T2D patients. In addition, we identified that rs2910164-C allele is associated with reduced expression levels of the miR-146a but not its mRNAs targets and cytokine levels in diabetic patients.
KeywordsMicroRNAs miR-146a rs2910164 Cytokines Diabetes
We greatly appreciate the assistance provided by the staff of the Endocrinology and Metabolism Research Institute of Tehran University of Medical Sciences. We also thank all volunteers for their participation in the study. This work was financially supported by a Grant (93-02-30-25172) from the Deputy of Research, Tehran University of Medical Sciences.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
The study was approved by Tehran University of Medical Sciences Ethics Committee and performed in compliance with Helsinki declaration.
Written informed consent was obtained from all subjects before enrollment in the study.
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