Prevalence of Mitochondrial tRNA Gene Mutations and Their Association with Specific Clinical Phenotypes in Patients with Type 2 Diabetes Mellitus of Coimbatore

Abstract

The association of mitochondrial DNA mutation with type 2 diabetes mellitus (T2DM) is well established. In this study we aimed to assess the frequency of A3243G, A8296G, and other mitochondrial mutations with reference to clinical features in the diabetic population of Coimbatore, India. The study group included 150 patients (89 women and 61 men) with T2DM, whereas the control group included 100 nondiabetic people (59 women and 41 men). Genotyping was done by polymerase chain reaction followed by single-strand confirmation polymorphism method. A3243G and A8296G mutations were found to be prevalent in patients with T2DM when compared with the control group. The A3243G mutation was found in two patients, and both these patients showed similar clinical characteristics, thus representing a putative clinical subtype. A8296G mutation was detected in one patient. The same mutation was shared with his mother who was diagnosed to have diabetes mellitus (DM) with neuromuscular disorder. The siblings of the patient did not show any symptoms of DM. Lipid profile and urea and creatinine levels were found to be significantly high (10% and 0.064%) in patients with T2DM compared with control subjects. We concluded that the identification of these mitochondrial point mutations indicates a new genetic predisposition of DM in Coimbatore population.

Mitochondrial complex I and V gene polymorphisms in type II diabetes mellitus among high risk Mizo-Mongoloid population, Northeast India

“…Earlier reports showed the association of mitochondrial DNA mutations like 1310C < T, 1382A < C, 1438G < A, 1201A < G, 3243A < G, 3252A < G, 3256A < T, 3264A < C, 3271A < C, 3290T < C, 3303C < T, 3316G < A, 3394T < C, 8296A < G, 8344A < G, 11778G < A, 12026A < G, 12258C < A, 14577T < C, 14709T < C and 16189T < C [ 16 – 20 ] with T2D development. Particularly, mutation in tRNA Leu gene at 3243 (A < G) position and in the subunits of NADH dehydrogenase 1 and 4 have been reported to have strong association with incidence of diabetes in different populations [ 18 , 19 , 21 , 22 ]. There was a significant correlation between the number of somatic mtDNA ATP6 mutations and the smoking and consuming betel-nut with paan (OR: 3.52; 95 % CI: 0.96–12.11) for the type 2 diabetes along with drinking alcohol (OR: 4.62; 95 % CI: 1.82–14.53).…”

Screening of mitochondrial mutations and insertion–deletion polymorphism in gestational diabetes mellitus in the Asian Indian population

“…Duraisamy et al, 2010 performed a mitochondrial study of the A3243G variant in South Indian T2DM patients. The variant was identified in two patients with similar clinical characteristics.…”

“…The variant was identified in two patients with similar clinical characteristics. They concluded that these mitochondrial mutations indicate a genetic predisposition to DM in the Coimbatore South Indian population (Duraisamy et al, 2010). In our study, we found eleven mutations in the GDM cases and three in the non-GDM subjects.…”

“…More than 50% of these mtDNA mutations are located in 22 mitochondrial tRNA genes, including tRNA Leu(UUR) (Li and Guan, 2010). mtDNA mutations have been described in association with various diseases, including T2DM (Li and Guan, 2010; Mathews and Berdanier, 1998; Duraisamy et al, 2010; Padma et al, 2010). The involvement of mtDNA in disease pathogenesis could contribute to biased maternal transmission of certain forms of diabetes.…”

Mitochondrial ND1 gene mutation analysis in type II diabetes of Karaikudi population

“…Mitochondria play an imperative role in glucose metabolism, insulin secretion and biogenesis, hence its dysfunction is reportedly found to play a crucial role in diabetes development (Gerbitz et al 1996;Choo Kang et al 2002). Earlier reports showed the association of mitochondrial DNA mutations like 1310C [T, 1382A[C, 1438G[A, 1201A[G, 3243A[G, 3252A[G, 3256A[T, 3264A[C, 3271A[C, 3290T[C, 3303C[T, 3316G[A, 3394T[C, 8296A[G, 8344A[G, 11778G[A, 12026A[G, 12258C[A, 14577T[C, 14709T[C and 16189T[C (Giles et al 1980Alcolado et al 1994;Kalinin et al 1995;Seneca et al 1998;Chinnery et al 2000;Hattori et al 2003;Pranoto 2005;Brandon et al 2005;Liu et al 2007;Mezghani et al 2010;Vijaya Padma et al 2010;Duraisamy et al 2010;Weng et al, 2013) with T2D development. Particularly, mutation in tRNA Leu gene at 3243 (A[G) position and in the subunits of NADH dehydrogenase 1 and 4 have been reported to have strong association with diabetes incidence in different populations (Kalinin et al 1995;Zhao and Zhang 2001;Lam et al 2001;Pranoto 2005;Yu et al 2004;Duraisamy et al 2010;Vijaya Padma et al 2010).…”