Lack of association of mitochondrial A3243G tRNALeu mutation in Iranian patients with type 2 diabetes

Document Type : Research Paper


1 Department of Medical Genetics, National Institute for Genetic Engineering and Biotechnology (NIGEB), Tehran, I.R. Iran.

2 Research and Sciences Unit, Azad Islamic University, Tehran, I.R. Iran.

3 Endocrinology and Metabolism Research Center, Tehran University of Medical Sciences. Tehran, I.R. Iran.


Many kinds of mutations in mitochondrial (mt) DNA have been reported to be related to the development of Diabetes Mellitus (DM), this type of diabetes has also been shown to be influenced by other genetic factors and/or environmental factors. Among them, tRNALeu(UUR) and its adjacent mtDNA NADH dehydrogenase subunit 1(ND1) region within the mt genome are linked to high susceptibility to DM. A point mutation at 3243 base pair (bp) in the mt tRNA Leu(UUR) is commonly referred to as a syndrome of mitochondrial myopathy, Encephalopathy, Lactic acidosis, and Stroke-like episodes (MELAS). In the current study, we have assessed
the frequency of the A3243G in Iranian diabetic type 2 patients. DNA was obtained from peripheral leukocytes of 154 patients with diabetes Mellitus type2 (l50 with type 2 and 4 with gestational diabetes) and 40 control subjects. Insulin concentration from patients’ blood was measured using Radioimmunoassay procedure. Patients showed fasting blood sugar (FBS) between 150-230 mg/dl, body mass index (BMI) between 19-32 Kg/m2 and insulin concentration 0.9-2.35 mg/ml. PCR-RFLP, single strand conformation polymorphism
(SSCP) and sequencing methods were used to detect the A3243G or other mutations in the mitochondrial
tRNALeu (UUR) gene. A3243G mutation was not detected in patients. SSCP results showed a new pattern of PCR product in 6 patients. The C3316T transition mutation in the ND1 mitochondrial gene was confirmed in selected samples (n=6) by sequencing. No differences were observed between the two groups for C3316T and A3243G mutations (P=0.348). The mt C3316T mutation did not have any effect on the clinical finding of type 2 diabetes carrying this mutation. These data together with clinical characteristics of the patients may
suggest that the mt C3316T mutation might be a polymorphism in the Iranian population.