The Assessment of Mitochondrial Trnaleu(UUR) A3243G Mutation and Their Association with Oxidative Stress among Patients with Inherited type 2 Diabetes Mellitus: A Case Control Study

Abstract

Introduction/Background: Transfer RNA (tRNA) genes in the mitochondrial DNA genome play an important role in protein synthesis. Insulin secretion does not occur because the mitochondria cannot work optimally. tRNA mutation may also be caused by insulin resistance. In addition, the loss of tRNA modification can cause pancreatic β cell dysfunction. The knowledge about the association of A3243G mitochondrial gene mutation with oxidative/antioxidative systems in the familial T2DM is limited which prompted us to conduct this study.

Objective: To compare the status of mitochondrial gene variant A3243G with oxidative stress markers in familial T2DM as well as in healthy controls, and to find out the association between the parameters, if any

Materials and Methods: A total of 180 subjects (study group: 120; control group: 60) were included in the study. Patients, who attended the Department of Endocrinology and Metabolism, SS Hospital, IMS, BHU, were on diabetes treatment and had a familial history of DM, comprised the study group. Patients underwent clinical, molecular and biochemical assessments. The mtDNA genes were PCR amplified and sequenced. Mitochondrial adenosine triphosphate (ATP) and reactive oxygen species (ROS) were measured

Results: When compared to the control group, greater penetrance was observed among the T2DM patients residing in urban areas (p = 0.038). Among the biochemical parameters, no significant difference was found in the level of Hemoglobin (Hb) among both the study groups (p = > 0.50), whereas values of FPG and HbA1c were found significantly higher among T2DM subjects compared to control subjects (p = < 0.001 and p = < 0.001 respectively). Among the oxidative stress markers, the peripheral blood TOS and OSI were found to be significantly higher among T2DM subjects than control subjects (p = < 0.001). When compared with the control subjects the peripheral blood TAS level were found to be significantly lower among the T2DM patients (p = < 0.001). A positive correlation was found between the FPG and HbA1c levels (p = < 0.01) and HbA1c and TOS levels (p = < 0.01), whereas a negative correlation was found between TOS and TAS levels (p = < 0.001) and HbA1c and TAS levels (p = < 0.05) Out of total 120 T2DM patients, three patients were found to carry the A3243G mutation in the mitochondrial tRNALeu(UUR) gene in the heteroplasmic form

Conclusion:  Antioxidants play an integral role in prevention of metabolic syndrome, DM, and associated complications hence including antioxidant-rich foods in the diet can possibly avoid or atleast delay the occurrence of such complications. The mitochondrial A3243G mutation in the mitochondrial tRNALeu(UUR) gene was found with low frequency but was comparable with previous studies. However screening of large study group with additional screening for mtDNA mutations other than A3243G mutation can further unravel the epidemiological dynamics and prevalence of MIDD or mtDM.