A Common Mitochondrial DNA Variant and Increased Body Mass Index as Associated Factors for Development of Type 2 Diabetes: Additive Effects of Genetic and Environmental Factors

Abstract

The mtDNA 16189 variant can influence development of T2DM. The demonstrated dynamic between the 16189 variant and increased BMI exemplify an additive effect of genetic and environmental factors on the pathogenesis of T2DM.

A mitochondrial DNA variant at position 16189 is associated with type 2 diabetes mellitus in Asians

“…Despite the negative results in a meta-analysis of European studies [10], consistent with other studies [4,5,9], we found an association between the 16189C variant and the risk of type 2 diabetes in this multinational Asian case-control cohort. The substitution of cytosine for thymidine at np 16189 results in a poly-cytosine tract (the 16184-16193 poly-C tract).…”

“…Taken together, our data suggest that differences in nuclear and mitochondrial genetic backgrounds between Europids and Asians may contribute to differences in susceptibility to type 2 diabetes, often in combination with environmental factors. In support of this notion, increased BMI has been shown to be an aggravating factor for the development of diabetes in individuals with the 16189C variant [9].…”

“…1]. We performed a metaanalysis after combining the current data with three additional datasets from other Asian studies [7][8][9], to give a total of 3,283 cases with diabetes and 2,176 controls (Fig. 1).…”

“…Mutations in mitochondrial DNA (mtDNA) have been reported to be a cause of maternally inherited diabetes mellitus [2] and a cluster of features of the metabolic syndrome [3]. The cytosine for thymidine substitution (T→C) at nucleotide position (np) 16189, which lies in the mtDNA control region for replication and transcription, has been reported to be associated with insulin resistance and type 2 diabetes [4][5][6][7][8][9]. Despite these findings, a recent meta-analysis of European studies concluded that the 16189C variant was not associated with type 2 diabetes in Europids [10].…”

Effects of mitochondrial haplogroup N9a on type 2 diabetes mellitus and its associated complications

“…The common variants or mitochondrial haplogroups of single mitochondrial DNA (mtDNA) mutations, such as major rearrangements (8) and point mutations (9), may modulate the mitochondrial function and thereby be associated with the development of certain conditions. A T-to -C transition at nucleotide pair 16,189, causing a homopolymeric tract of cytosines at nucleotide pairs 16,193, was confirmed to accompany the susceptibility to T2DM in certain ethnic groups (10,11). Furthermore, mitochondrial haplogroups have been suggested to contribute to the susceptibility to T2DM and obesity.…”