Balkan Journal of Medical Genetics

EPIGENETIC ALTERATIONS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS
Karachanak-Yankova S1,a, Dimova R2,a, Nikolova D1, Nesheva D1, Koprinarova M3, Maslyankov S4, Tafradjiska R5, Gateva P6, Velizarova M7, Hammoudeh Z1, Stoynev N2, Toncheva D1, Tankova T2, Dimova I1,*
*Corresponding Author: Ivanka Dimova, Associate Professor, Department of Medical Genetics, Medical University Sofia, Zdrave str. 2, 1431 Sofia, Bulgaria. Tel: +359-2-91-72-735. E-mail: ivanka.i.dimova@ gmail.com
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RESULTS

Expression Profile of MBD2 in Patients with T2DM. The gene expression analysis of MBD2 performed for each of the 12 controls and 16 T2DM patients revealed a 10.4-times increase on average in MBD2 mRNA levels in patients compared to controls (Figure 1a). The separate analysis in each patient group showed the highest increase in the newly-diagnosed (treatment-naïve) T2DM patients; 12.9-times average increase, followed by 10.4-times average increase in patients with T2DM duration of less than 5 years and 6.1-times average increase in T2DM patients with duration of the disease of more than 5 years (Figure 1b to 1d). Methylation Analysis of Genes Connected to Stress and Toxicity in Patients with T2DM. Using EpiTect Methyl II Signature PCR Array (Qiagen Sciences Inc.), the methylated and non methylated fraction of 11 genes, connected to cellular response to stress and toxicity, were successfully analyzed in all DNA pools. The methylation fraction of these genes is represented in Table 3. In the healthy controls, the methylated fraction was 0% in six of the analyzed genes, ranged from 1.4 to 7.3% in four genes and was 98.5% for the GDF15 gene. In newly-diagnosed T2DM patients, the methylated fraction was 0% only in one gene, 98.4% in GDF15 and increased to values between 4.9 and 23.6% for the remainder of the genes. In patients with T2DM duration of less than 5 years, the methylated fraction was 97.7% for GDF15 and varied between 0.5 and 22.4% for all other genes. Among T2DM patients with duration of more than 5 years, the methylated fraction was 0% in two of the analyzed genes, 95.9% for GDF15 and ranged from 7.6 to up to 47.8% for the rest of the genes. The genes Gadd45G, Gpx3 and RARA showed the highest methylated fraction in newly-diagnosed T2DM patients, probably due to the poor glycemic control. Five genes were with consistently increased methylated fraction during the course of the disease: BRCA1, CCND1, Prdx2, SCARA3 and Tp53 (Figure 2). There was a slight decrease in the methylated fraction of GDF15 with increase in the duration of T2DM.

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