Mitochondrial gene mutations in gestational diabetes mellitus

Mitochondrial DNA mutations have been implicated in many diseases including diabetes mellitus. Although gestational diabetes,mellitus (GDM) has been s uggested to have genetic determinant and to be etiologically indistinct wit h non-insulin-dependent diabetes mellitus (NIDDM), its association with mit ochondrial gene mutations is still unknown. In this study, 137 patients wit h GDM and 292 non-diabetic pregnant controls were examined for mitochondria l DNA mutations from the nucleotide 3130-4260 encompassing tRNA-Leu gene an d adjacent NADH dehydrogenase 1 gene by polymerase chain reaction, single-s tranded conformation polymorphism, restriction fragment length polymorphism and DNA sequencing. One heteroplasmic mutation at the position of 3398 (T- C), which changed a highly conserved methionine to threonine in NADH dehydr ogenase subunit 1, was identified in 2.9% GDM patients but not in the contr ols, indicating its association with GDM (P = 0.01). Two novel mutations, a heteroplasmic C3254A and a homoplasmic A3399T, were also found in GDM subj ects, the functional meaning of which merits further investigation, G3316A and T3394C mutations implicated in NIDDM, were seen at higher frequencies i n patients with GDM than the controls. Our results suggest that mitochondri al DNA mutations may contribute to the development of GDM in some patients. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.