Purpose: Abnormal optic disc excavations are found in patients with Leber's hereditary optic neuropathy (LHON). The purpose of this study was to determine whether heteroplasmy for the major three LHON mutations or for the rare LHON mutations are risk factors for open-angle glaucoma.
Methods: Blood samples from 835 Japanese subjects were screened with the Invader assay for ten LHON-associated mutations: three major mutations (G3460A, G11778A, T14484C) and seven rare mutations (T9101C, G9804A, C14482A, C14482G, G14459A, T14498C, and A14510G). Of the 835 subjects, 241 were patients with primary open-angle glaucoma (POAG), 310 were patients with normal-tension glaucoma (NTG), and 284 were healthy controls.
Results: Five POAG patients and three NTG patients had one of five mutations, C9099A, T9101G, T9101C, G9804A, or G11778A, but none of these patients had LHON. The C9099A (Ile191Met) and T9101G (Ile192Ser) mutations were novel and identified within the probes by lack of signal in the assay. Two patients with the G11778A mutation showed heteroplasmy, with 15% mutant mtDNA in the male patient and 80% in the female patient. The remaining LHON-associated mutations were not detected in any of the subjects. A case-control study did not show a significant difference (P = 0.099): eight potentially disease-associated variants in 551 patients versus zero variants in the 284 controls.
Conclusions: Rare LHON-associated mitochondrial DNA mutations were found in Japanese patients with open-angle glaucoma (OAG). However, whether mitochondrial DNA mutations are risk factors for OAG is still open to question.