BACKGROUND: Leber hereditary optic neuropathy (LHON) is an inherited form of 
bilateral optic atrophy leading to the loss of central vision. The primary cause 
of vision loss is mutation in the mitochondrial DNA (mtDNA), however, unknown 
secondary genetic and/or epigenetic risk factors are suggested to influence its 
neuropathology. In this study folate gene polymorphisms were examined as a 
possible LHON secondary genetic risk factor in Iranian patients.
METHODS: Common polymorphisms in the MTHFR (C677T and A1298C) and MTRR (A66G) 
genes were tested in 21 LHON patients and 150 normal controls.
RESULTS: Strong associations were observed between the LHON syndrome and C677T 
(P= 0.00) and A66G (P= 0.00) polymorphisms. However, no significant association 
was found between A1298C (P =0.69) and the LHON syndrome.
CONCLUSION: This is the first study that shows MTHFR C677T and MTRR A66G 
polymorphisms play a role in the etiology of the LHON syndrome. This finding may 
help in the better understanding of mechanisms involved in neural degeneration 
and vision loss by LHON and hence the better treatment of patients.