Genetic Indices Relationship to Hyperglycemia-associated Biomarkers: Consistency with miRNA Expression in Egyptian Children with T1DM

Abstract

Objective: Micro RNAs (miRNAs) are gaining acceptance as novel biomarkers for the autoimmune disorders. However, miRNA profiles have not been investigated in individuals at risk of or diagnosed with type 1 diabetes mellitus (T1DM). To study the expression pattern of miRNAs in plasma obtained from patients with T1DM and compare with matched healthy controls.

Methods: Equal numbers of patients with T1DM (90) and healthy-matched control children (90) were assessed for the expression profile of plasma miRNAs including miRNA-101-5p, miRNA-146-5p, miRNA-21-5p, miRNA-375, miRNA-126, and Let7a-5p using reverse transcriptase polymerase chain reaction methodology and quantitative real-time testing.

Results: Analysis showed that miRNA-101, miRNA-21 and miRNA-375 were highly expressed, whereas, miRNA-146-5p, miRNA-126, and miRNA-Let7a-5p showed significantly low levels of expression in T1DM patients compared to controls (p<0.05). In addition, miRNA-101 and miRNA-146 correlated with age at diagnosis of T1DM and disease duration, respectively. Furthermore, multivariate analysis showed that miRNA-126 and Let7a-5p had a significant negative correlation with mean hemoglobin A1c (HbA1c) values.

Conclusion: Dysregulation of the six miRNAs analyzed suggested a possible role as biomarkers in T1DM. miRNA-101 was correlated with age at diagnosis while miRNA-146 correlated with disease duration. Two further miRNAs correlated with the existing biomarker, HbA1c.

Keywords: Type 1 diabetes; gene expression; miRNAs; plasma; q RT-PCR.

Figure 1

a) Correlation results between miRNA-101-5p with age of type 1 diabetes mellitus onset. b) Correlation results between miRNA-126 and hemoglobin A1c

Figure 2

Amplification plot for miRNA-21-5p expression pattern [normalized fluorescent signal (ΔRn) plotted against the number of the cycle]

Figure 3

a) Amplification for miRNA-101-5p expression [normalized fluorescent signal (ΔRn) plotted against the number of the cycle]. b) Amplification for miRNA-146a-5p expression [normalized fluorescent signal (ΔRn) plotted against the number of the cycle]

Figure 4

a) Amplification for miRNA-375 expression [normalized fluorescent signal (ΔRn) plotted against the number of the cycle]. b) Amplification plot of miRNA Let 7 a-5p expression [normalized fluorescent signal (ΔRn) against the number of the cycle]

Figure 5

a) Amplification of miRNA-126 gene expression [normalized fluorescent signal (ΔRn) against the number of the cycle]. b) Amplification of miRNA-126 gene expression [normalized fluorescent signal (ΔRn) against the number of the cycle]