Phylogenetic analysis of mitochondrial DNA in type 2 diabetes - Maternal history and ancient population expansion

Several studies hare suggested a maternal excess in the transmission of typ e 2 (non-insulin-dependent) diabetes. However, the majority of these report s rely on patients recalling parental disease status and hence are open to criticism. An alternative approach is to study mitochondrial DNA (mtDNA) li neages, The hypervariable region 1 of the rapidly evolving noncoding sectio n of mtDNA is suitable for investigating maternal ancestry and has been use d extensively to study the origins of human racial groups. we have sequence d this 347-bp section of mtDNA from leukocytes of subjects with type 2 diab etes (n = 63) and age- and race-matched nondiabetic control subjects (n 57) . Consensus sequences for the two study groups were identical. Pairwise seq uence analysis show ed unimodal distribution of pairwise differences for bo th groups, suggesting that both populations had undergone expansion in anci ent times. The distributions were significantly different (chi(2) = 180, df = 11, P < 0.001); mean pairwise differences were 4.7 and 3.8 for the diabe tic and control subjects, respectively. These data suggest that the diabeti c subjects belong to an ancient maternal lineage that expanded before the m ajor expansion observed in the nondiabetic population. Phylogenetic trees c onstructed using maximum parsimony, neighbor-joining, Fitch-Margolish, or m aximum Likelihood methods failed to show the clustering of all (or a subset ) of the diabetic subjects into one or more distinct lineages.