Multiple skeletal muscle mitochondrial DNA deletions in patients with unilateral peripheral arterial disease

Peripheral arterial disease (PAD) is associated with metabolic derangements and accumulation of the common 4977 bp mitochondrial DNA (mtDNA) deletion mutation. The current study was undertaken to test the hypothesis that PAD is associated with multiple mtDNA deletions. Gastrocnemius biopsies were ob tained from nine patients with unilateral PAD. DNA extracted from the biops ies was analyzed for mtDNA deletions using a primer-shift PCR strategy. Mul tiple primers and strict, prospective criteria were used to identify deleti ons. PAD was associated with multiple mtDNA deletions (average of 8.2 disti nct deletions in muscle from the hemodynamically affected limb). mtDNA inju ry was present in both the worse- and less-affected limbs of the unilateral PAD patients, and the estimated degree of mtDNA injury was strongly correl ated in the two limbs on an intra-subject basis. The 4977 bp deletion was f requently identified, but was not always the deletion of highest frequency in individual samples. The estimated relative frequency of the 4977 bp dele tion was correlated with the overall mtDNA injury in the biopsies. In summa ry, PAD is associated with mtDNA injury as reflected by multiple deletion m utations. As the mutations are not limited to the ischemic limb in unilater al patients, they are unlikely to contribute to the pathophysiology of clau dication.