C677T methylene-H4-folate-reductase variant decreases binocular accommodation.
OBJECTIVE
The C677T polymorphism of methylene tetrahydrofolate reductase (MTHFR) lowers the activity of this enzyme, producing moderate elevation of blood levels of homocysteine (Hcy) and lowering the levels of 5-methyl-tetrahydro-folic acid (5-MeTHFA), methionine (Meth), and S-adenosylmethionine (SAM). In this study we examined 100 apparently normal subjects of both sexes (average age 25.6 +/- 4.25) for the genotypic presence of the T allele and its association with accommodative amplitude (AA).


METHODS
The amplitude of accommodation was measured by the subjective "push-up" technique. DNA from buccal cells was genotyped for the C677T polymorphism of MTHFR by a PCR-restriction fragment length polymorphism genotyping assay. Descriptive statistics were obtained by frequency distribution and univariate analysis. Comparisons between monocular and binocular AA were obtained by t-test statistics or ANOVA. Associations between genotype and phenotype were analyzed using regression models.


RESULTS
The C677T polymorphism was associated with decreased binocular AA (p = 0.0087). Monocular AA was not associated with the MTHFR genotype.


CONCLUSIONS
Our results suggest a role for the C677T polymorphism in damaging the neural aspects of binocular vergence accommodation. The postulated neural damage could be due to the decreased formation of 5-MeTHFA and the defective synthesis of Meth, SAM and neurotransmitters or other methyl acceptors in nervous tissue of bearers of the C677T polymorphism. The differential effect upon monocular and binocular accommodation is hypothetically explained by a greater involvement of methylation reactions in vergence accommodation. A similar mechanism is proposed to explain the prevalent insufficient accommodation of Down's syndrome in which the blood levels of Meth and SAM are reduced.
Krumdieck
Carlos L
CL
Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA. clkb@uab.edu
Fernandez
Jose R
JR
Desmond
Renee A
RA
Kleinstein
Robert N
RN
Shipp
Melvin D
MD
Prince
Charles W
CW
D000065:Accommodation, Ocular / Q000235:genetics*; D000328:Adult; D005260:Female; D005492:Folic Acid / Q000097:blood; D014644:Genetic Variation; D005838:Genotype; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D015348:Vision, Binocular / Q000235:genetics*
D006710:Homocysteine; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2)