Mutation in the mitochondrial tRNAleu at position 3243 and spontaneous abortions in Japanese women attending a clinic for diabetic pregnancies

Abstract

SummaryMitochondrial DNA is exclusively maternally inherited. We recently found the prevalence of diabetic patients with an A to G transition at position 3243 of leucine tRNA (3243 base pair (bp) mutation) to be nearly 1% in randomly selected Japanese subjects. Here, we report the higher prevalence of diabetic patients with the 3243 bp mutation in a specific Japanese population of women attending a diabetic pregnancy clinic. Of 102 patients with non-insulin-dependent diabetes mellitus 6 (5.9 %) were positive for the mutation, 1 (8.3 %) of 12 patients with gestational diabetes and 2 (5.9 %) out of 34 borderline diabetic patients. In contrast, none of 64 patients (0 %) with insulin-dependent diabetes mellitus had the 3243 bp mutation. Moreover, there was a difference in the prevalence of spontaneous abortions between patients with and without this mutation (27.3 vs 12.4%). Among nine probands with the mutation, four had a history of one spontaneous abortion (p = 0.0518) and two had a history of two abortions (p = 0.0479). Two probands had a spontaneous abortion even while under strict diabetic metabolic control. The 3243 bp mutation thus may cause spontaneous abortion during pregnancy. [Diabetologia (1995) 38: 809-815] Key words Mitochondrial DNA mutation, insulin-dependent diabetes mellitus, non-insulin-dependent diabetes mellitus, gestational diabetes mellitus.It is well-known that one of the main causes of spontaneous abortion is an abnormality in the fetus rather than a problem in the mother [1]. The prevalence of abortion in diabetic women is higher in the high-titre HbAI: group during the first trimester [2,3]. Pre-pregnancy education courses are available in diabetic pregnancy clinics in Japan, and diabetic mothers are instructed to keep postprandial blood

Prevalence of mitochondrial DNA disease in adults

“…[15][16][17][18][19][20][21][22] Majamaa and colleagues 22 detected a prevalence of clinically affected individuals with m.3243AϾG of 5.71 in 100,000 (95% confidence interval, 4.53-6.89/100,000) but did not detect a single individual with m.8344AϾG. The reason for the difference from our data is not clear, although differences in the respective genetic backgrounds, population structures, and study design may be important.…”

Genetics of Gestational Diabetes Mellitus

“…No evidence of association was found neither in Singaporean women nor in predominantly Caucasians women from the US [254,255]. However, it was found in 1 of 12 Japanese women with GDM [256]. On the other hand, the T3398C mutation in the mitochondrial ND1 gene was more common in Singaporean women with GDM compared to pregnant controls (2.9 vs. 0%) [255].…”

Genotypic and phenotypic differences between Arabian and Scandinavian women with gestational diabetes mellitus

“…The A3243G mutation was reported in one of twelve Japanese women with GDM [15]. A T to C substitution at nucleotide 3398 in the mitochondrial ND1 gene was associated with GDM in women from Singapore [14].…”

“…To date, several genetic studies have been carried out to identify susceptibility genes predisposing for the development of GDM. Associations have been reported between GDM and variants in the glucokinase [13], mitochondrial DNA [14,15], β 3 -adrenergic receptor [16], sulphonylurea receptor 1 (SUR1) [17], insulin receptor and insulin-like growth factor 2 (IGF2) genes [18]. Some of these associations have not been replicated [19,20].…”