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

Lancet. 2000 Dec 16;356(9247):2068-9. doi: 10.1016/s0140-6736(00)03408-5.


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 tRNA(Leu(CUN)) was able to ameliorate the A3243G-induced biochemical phenotype. We analysed the tRNA(Leu(CUN)) gene in 48 unrelated A3243G cases. We showed that a polymorphism, A12308G, in tRNA(Leu(CUN)) increases the risk of developing stroke in patients with the A3243G mutation (relative risk=2.17). This may have implications for genetic counselling.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Mutational Analysis
  • DNA, Mitochondrial / genetics*
  • Haplotypes
  • Humans
  • MELAS Syndrome / complications
  • MELAS Syndrome / genetics*
  • Phenotype
  • Point Mutation*
  • Polymorphism, Genetic*
  • RNA, Transfer, Leu / analysis
  • RNA, Transfer, Leu / genetics*
  • Stroke / complications
  • Stroke / genetics*


  • DNA, Mitochondrial
  • RNA, Transfer, Leu