Hyperhomocysteinemia and the methylenetetrahydrofolate reductase 677C-T mutation in patients under 50 years of age affected by central retinal vein occlusion.

Purpose: To investigate the correlation between increased homocysteine plasma levels and the homozygosity for the 677C-T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene in patients aged under 50 years affected by central retinal vein occlusion (CRVO).

Design: Prospective, case-control study.

Participants And Controls: Participants included 31 consecutive patients under 50 years and diagnosed with CRVO. Two controls per case were selected. The first control group (group I) included 31 individuals matched for age, gender, laboratory tests, and the main risk factors for atherosclerosis. The second control group (group II) consisted of 31 volunteers matched only for age and gender.

Methods: Fasting (>10 hours) blood samples were obtained from patients and controls. Blood samples were obtained from patients within 1 week after the onset of the vaso-occlusive event. Molecular genetic analysis for the 677C-T mutation in the MTHFR gene was performed in patients and controls. A plasma homocysteine reading of >12 micromol/l was considered an increase.

Main Outcome Measures: The total homocysteine plasma level (determined by the high-performance liquid chromatography method with fluorescence detection) and molecular genetic analysis for the 677C-T mutation in the MTHFR gene in patients and controls.

Results: Mean ages were 44.5 years in the group comprising the patients and 44.3 and 44.2 years, respectively, in groups I and II. Mean homocysteine plasma levels were 10.60 micromol/l in patients and 10.39 and 9.34 micromol/l, respectively, in groups I and II. There was no statistically significant difference between mean homocysteine plasma levels in patients and group I controls. In fact, the mean homocysteine plasma level was lower in group II than in patients, and the difference was statistically significant. Homozygosity for the 677C-T mutation in the MTHFR gene was found in 4 patients (12.9%), 5 controls in group I (16.1%), and 4 controls in group II (12.9%).

Conclusion: The results of the present investigation support the hypothesis that the homocysteine plasma level is not to be considered a primary and independent risk factor for CRVO, but is more likely a marker of atherosclerosis and the consequence of other well-established risk factors. Moreover, the importance of the study design is brought out, because the results we obtained differ on the basis of the considered control group. This feature may in part explain the contradictory results reported in the literature.