Journal of Clinical and Diagnostic Research. 2023 Jan, Vol-17(1): BC11-BC14 11 11 DOI: 10.7860/JCDR/2023/53508.17344 Original Article Biochemistry Section Evaluation of Oxidative DNA Damage among Type 2 Diabetes Mellitus Patients and Healthy Individuals in Duhok, Iraq: A Case-control Study INTRODUCTION Cellular dysfunction occurs as a result of proteins and lipids oxidation as well as DNA modifications [1]. When DNA repair system and endogenous antioxidant network are overwhelmed, oxidative DNA damage occurs [2]. Association between oxidative stress and DNA damage has been reported [3]. Some studies have shown that oxidative stress plays an important role in cellular injury through persistent increased blood sugar [4,5]. The data regarding association of increased glucose and amount of DNA damage are controversial [6,7]. Numerous studies showed an increase in DNA damage in patients with type 2 Diabetes Mellitus (DM) when compared with apparently healthy subjects [8,9]. Persistent hyperglycemia can produce large amount of free radicals [10]. Because the body's defenses are inadequate to deal with the increased production of Reactive Oxygen Species (ROS), an imbalance between ROS production and their defenses develops. This results in oxidative stress [10]. These substances that are produced can cause breaks in the strands of DNA molecule as well as cause base modification, including guanine residues oxidation which is most potential base in DNA molecule that is oxidized more than other bases because of imidazole ring in its structure and leads to 8-OHdG production that is an oxidized nucleoside of DNA. The DNA damage by oxidation has been demonstrated by measuring the 8-OHdG levels, a known marker of oxidant induced DNA damage, in diabetic subjects [3,11]. The most frequent studied and detected biomarker of oxidative DNA damage is 8-OHdG [8,12]. Recently, numerous clinical studies have studied levels of 8-OHdG in human organs, leukocyte DNA and urine concerning oxidative stress and diabetes mellitus [8,13]. Since 8-OHdG is an established biomarker of oxidative DNA damage [14], it is pivotal to study the association of oxidative DNA with other related factors such as lipid oxidation by-product (such as MDA) and total antioxidant capacity in patients with type 2 DM and healthy individuals. To the author's knowledge little data are available in this area investigating oxidative stress and DNA damage in patients with diabetes [8]. This study is a part of previously published study [8]. Thus, this study was conducted to assess oxidative DNA damage, as well as antioxidant capacity in patients with type 2 DM and healthy individuals in Duhok, Kurdistan Region (Iraq). MATERIALS AND METHODS This case-control study was conducted at the Duhok Diabetes Center, Duhok, Kurdistan Region, Iraq, from September 2016 to March 2018. Medical Ethics Committee approval (Reference No: 07062016-4) and informed written consent was obtained for all participants. HIVI MOHAMMED MAHMOUD 1 , ARDAWAN FATHI ALI 2 , WAHID MOHAMMED HASSAN 3 , IDRIS HAJI AHMED 4 , DHIA JAAFER ALTIMIMI 5 Keywords: Deoxyribonucliec acid, 8-hydroxy-2-deoxiguanosine, Diabetes mellitus, Malondialdehyde, Oxidative stress, Total antioxidant capacity ABSTRACT Introduction: The association between oxidative Deoxy Ribonucleic Acid (DNA) damage and diabetes is well established. Increased glucose levels can stimulate free radical production. However, data regarding DNA damage in type 2 Diabetes Mellitus (DM) patients and healthy individuals are controversial and scarce in Iraq. Aim: To assess the DNA damage among patients with type 2 Diabetes Mellitus (DM) and healthy individuals and to analyse its relationship with oxidative stress biomarkers. Materials and Methods: This case-control study was conducted at the Duhok Diabetes Center, Duhok, Kurdistan Region, Iraq, from September 2016 to March 2018. In this study, biomarkers of both oxidative stress and DNA damage including Total Antioxidant Capacity (TAC), Malondialdehyde (MDA) and serum 8-Hydroxy-2-deoxiguanosine (8-OHdG) were measured in 297 patients with type 2 diabetes and 188 healthy individuals. Selection of cases and healthy individuals was done using random sampling technique. Statistical analysis was done using Statistical Package for Social Sciences (SPSS) version 18.0 and a p-value <0.05 was set as a cut off value of statistical significance. Results: The mean age, sex and Body Mass Index (BMI) were similar between patients and healthy individuals. Significantly higher 8-OHdG and MDA levels (p<0.001 and p<0.010, respectively) together with lower TAC levels (p=0.010) were found in diabetics compared to healthy individuals. In diabetic patients, a positive correlation of 8-OHdG was observed with MDA (r=0.220), and a negative correlation was observed with TAC (r= -0.47). Based on the estimated cut-off point of DNA damage (8-OHdG of 4.0 ng/mL), 84.51% of patients had high levels of DNA damage compared with healthy individuals (28.7%). Conclusion: Oxidative DNA damage increased in diabetic patients, and was associated with lower antioxidant capacity. Antioxidant supplementation may be an effective public health intervention to reduce DNA damage and oxidative stress.