Journal
JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION
Volume 41, Issue 5, Pages 557-566Publisher
SPRINGER
DOI: 10.1007/s40618-017-0766-z
Keywords
MicroRNAs; miR-146a; rs2910164; Cytokines; Diabetes
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Funding
- Tehran University of Medical Sciences [93-02-30-25172]
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Purpose 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. Methods 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-alpha, IL-6, IL-10 and IL-1 beta serum levels were measured using ELISA method. Results 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 NF kappa B-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. Conclusion 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.
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