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Article type: Research Article
Authors: Ahmad, Jamal | Gupta, Anuj | Alam, Khursheed | Farooqui, Khalid Jamal
Affiliations: Centre for Diabetes and Endocrinology, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, U.P., India | Department of Medicine, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, U.P., India | Department of Biochemistry, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, U.P., India
Note: [] Corresponding author. Tel.: +91 571 2721544; Fax: +91 571 2721544; E-mail: jamalahmad11@rediffmail.com
Abstract: Aims: The vascular tissues have a long memory of their previous glycemic control and intervention studies have demonstrated that microvascular complications are highly correlated with mean glycemic control as measured by glycolated hemoglobin A_{1}C (HbA_{1}c). The present study was carried out to evaluate the autoantibodies against glycosylated DNA (DNA-AGEs) in diabetic sera to see if the level of HbA1c has correlation with the activity of DNA-AGEs, another marker of chronic glycemia. Methods: Glucose-6-phosphate induced glycosylation of native DNA was studied in 150 diabetic sera (T1DM=9, T2DM=141) by spectroscopic techniques (UV and fluorescence) and agarose gel electrophoresis. Direct binding and inhibition enzyme immunoassays were carried out to evaluate binding and specificity of anti-glycated-DNA autoantibodies (anti-DNA-AGE autoantibodies) in sera of diabetes patients. A quantitative estimation of HbA_{1c} was carried out in normal and diabetes sera. Results: Anti-DNA-AGEs autoantibodies in 55% of diabetic sera (85/150) showed more binding with glycated-DNA compared to native DNA which was subjected to inhibition ELISA indicating true interaction of these autoantibodies in diabetes with glycated DNA. Higher binding with glycosylated-DNA against native-DNA was observed in subjects with HbA1c of 9.8 ± 3.3% compared to those with HbA1c of 7.7 ± 1.7% (p< 0.001). Linear correlation analysis showed that mean absorbance difference was significantly related to HbA1c (r=0.486, p< 0.001), nephropathy (r= 0.239, p< 0.003), retinopathy (r=0.165, p< 0.05). Conclusions: Autoantibodies against glycosylated DNA were correlated with HbA_{1}c and microvascular complications and may be useful as another biomarker for assessment of chronic glycemia.
Keywords: Autoantibodies, glycosylated-DNA, diabetes mellitus
DOI: 10.3233/DMA-2011-0780
Journal: Disease Markers, vol. 30, no. 5, pp. 235-243, 2011
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