SCREENING FOR MTDNA DIABETES MUTATIONS IN PIMA-INDIANS WITH NIDDM

More than half of the Pima Indians over age 35 years have non-insulin- dependent (type II) diabetes mellitus (NIDDM). Extensive data indicate the importance of maternal diabetes in determining their risk for dia betes. Generally, the risk of having NIDDM is higher in patients with affected mothers than affected fathers. This has been attributed to in trauterine factors, but recently mitochondrial inheritance has been ra ised as an alternative hypothesis. In other populations, several famil ies and individuals with diabetes due to a mitochondrial DNA point mut ation at nucleotide 3243 in the tRNA(leu(UUR)), gene have been describ ed, as has one family with a 10.4 kb mitochondrial DNA duplication/del etion. We tested whether these specific mitochondrial gene mutations c ould explain a portion of the excess maternal transmission seen in the Pima Indians. Mitochondrial DNA obtained from blood lymphocytes of 14 8 Pima Indians with NIDDM was screened both for the point mutation at nt 3243, and the 10.4 kb duplication/deletion. Neither of these mutati ons was detected, and although a small proportion of the excess matern al transmission in Pima Indians could still be due to yet undescribed mitochondrial mutations or imprinted nuclear genes, our data support t he role of the intrauterine environment in this population. (C) 1995 W iley-Liss, Inc.