Association of Type 2 Diabetes with mt DNA A3245G gene Point Mutation – An Update

Abstract

ABSTRACT

Diabetes Mellitus (DM), a constantly occurring, multifactorial disorder, has victimized large groups of population all over the world. Apart from hormonal and metabolic defects, the responsible underlying molecular events for the development of the disease have been subjected to painstaking study during the last decades but despite the hard work, the basic essential events are yet to be discovered completely. Coordinated action of two genetic sources has been involved in biogenesis of efficient mitochondria i.e. mitochondrial and nuclear genome. In a nucleated somatic cell, entire mitochondrial DNA makes up to 0.5% of total DNA. Illustration of the entire human mtDNA sequence and cognition of its pathogenic mutations has made it easy and simple to appreciate the clinical implications of mtDNA mutations. Diabetes is a common and prominent manifestation of mtDNA mutation leading to impairment of Oxidative phosphorylation (OXPHOS). The most frequent diabetogenic heteroplasmic A3243G gene mutation is present on the MTTL1 gene encoding tRNA(Leu) (UUR). It is the major basis of DM of maternal heritage It is a major basis of maternally inherited diabetes mellitus associated with hearing defects– “Maternally Inherited Diabetes and Deafness (MIDD)”. A point mutation A3243G in the tRNALeu(UUR) gene is strongly associated with the development of Maternally Inherited T2D. Few Asian studies didn't show mitochondrial DNA mutation to be a main inducer of mitochondrial diabetes so other pathogenic factors responsible for T2D must be taken into account.