Increased risk of stroke in patients with the A12308G polymorphism in mitochondria

Factors which increase the risk of stroke in patients with the A3243G (mitochondrial encephalomyopathy, lactic acidosis, and stroke [MELAS]) mutation in human mitochondrial DNA are unclear. Previous work on lung-cancer cells with an A3243G mutation showed that a mutation in the mitochondrial transfer gene for leucine tRNALeu(CUN) was able to ameliorate the A3243G-induced biochemical phenotype. We analysed the tRNALeu(CUN) gene in 48 unrelated A3243G cases. We showed that a polymorphism, A12308G, in tRNALeu(CUN) increases the risk of developing stroke in patients with the A3243G mutation (relative risk=2·17). This may have implications for genetic counselling.