HETEROPLASMY LEVELS OF A MITOCHONDRIAL GENE MUTATION ASSOCIATED WITH DIABETES-MELLITUS DECREASE IN LEUKOCYTE DNA UPON AGING

We showed previously that a mutation in the mitochondrial tRNA(Leu(UUR )) gene at position 3243 associates with maternally inherited diabetes and deafness (MIDD). This mutation shows heteroplasmy in DNA from per ipheral blood and other tissues, To examine whether heteroplasmy level s in peripheral blood DNA change upon aging, heteroplasmy levels were determined in DNA samples from peripheral blood, collected recently an d 1,5-6 years ago, from 18 individuals carrying the 3243 mutation, It was found that 17 out of 18 carriers showed a decrease upon aging (P = 0.001), the average change being -0.69 +/- 0.61% per year, These data indicate a continuous selection against haematopoietic (precursor) ce lls carrying high levels of the 3243 mutation. Moreover, they imply th at heteroplasmy levels may decrease below the detection limit if DNA f rom peripheral blood is analyzed from elderly individuals. DNA from or al mucosa cells was found to be a good alternative as heteroplasmy lev els for the 3243 mutation are on the average 1.7 fold higher than in D NA from peripheral blood. (C) 1996 Wiley-Liss, Inc.