Genetic variation in the methylenetetrahydrofolate reductase gene, MTHFR, does not alter the risk of visual failure in Leber's hereditary optic neuropathy.
OBJECTIVE
Focal neurodegeneration of the optic nerve in Leber hereditary optic neuropathy (LHON) is primarily due to a maternally inherited mitochondrial DNA mutation. However, the markedly reduced penetrance of LHON and segregation pattern of visual failure within families implicates an interacting nuclear genetic locus modulating the phenotype. Folate deficiency is known to cause bilateral optic neuropathy, and defects of folate metabolism have been associated with nonarteritic ischemic optic neuropathy.


METHODS
Methylenetetrahydrofolate reductase (MTHFR) catalyzes a critical step in folate metabolism, and genetic variation in MTHFR has been associated with several late-onset neurodegenerative diseases.


RESULTS
We therefore determined whether functional genetic variants in MTHFR could account for the reduced penetrance in LHON by studying 414 LHON mtDNA mutation carriers. We found no evidence of association between visual failure in LHON and MTHFR polymorphisms or the MTHFR haplotype.


CONCLUSIONS
Genetic variation in MTHFR does not provide an explanation for the variable phenotype in LHON.
Mitochondrial Research Group, Institute of Ageing and Health, Newcastle University, Newcastle upon Tyne, UK.
Gavin
G
Hudson
Patrick
P
Yu-Wai-Man
Massimo
M
Zeviani
Patrick F
PF
Chinnery
D000328:Adult; D001766:Blindness / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D029242:Optic Atrophy, Hereditary, Leber / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide
D004272:DNA, Mitochondrial; D042965:Methylenetetrahydrofolate Reductase (NADPH2)