Thermolabile MTHFR genotype and retinal vascular occlusive disease
- M Cahill1001,
- M Karabatzaki1001,
- C Donoghue1002,
- R Meleady1003,
- L A Mynett-Johnson1002,
- D Mooney1001,
- I M Graham1003,
- A S Whitehead1004,
- D C Shields1005
- 1001The Research Foundation, The Royal Victoria Eye and Ear Hospital, Dublin 2, Ireland, 1002Department of Genetics, Trinity College, Dublin 2, Ireland, 1003Department of Cardiology, The Adelaide-Meath Hospital incorporating The National Children's Hospital, Tallaght, Dublin 24, Ireland, 1004Department of Pharmacology and Center for Pharmacogenetics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6084, USA, 1005Department of Clinical Pharmacology, The Royal College of Surgeons in Ireland, St Stephen's Green, Dublin 2, Ireland
- Dr M Cahill, Beetham Eye Institute, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215, USA mark.cahill@joslin,harvard.edu
- Accepted 8 August 2000
BACKGROUND Raised levels of total plasma homocysteine (tHcy) are associated with an increased risk of retinal vascular occlusive disease. A thermolabile form of a pivotal enzyme in homocysteine metabolism, methylenetetrahydrofolate reductase (MTHFR), has been associated with vascular occlusive disease and raised tHcy levels. The relation between thermolabile MTHFR genotype, tHcy, and retinal vascular occlusive disease has not been determined.
METHODS A retrospective case-control study involving hospital based controls and cases with retinal vascular occlusions in whom tHcy levels had been determined was undertaken. Genotyping for the MTHFR 677 C-T mutation that specifies the thermolabile form of the enzyme was performed by established methods in all subjects. The relation between homozygosity for thermolabile MTHFR genotype (TT), raised tHcy levels, and risk of retinal vascular occlusive disease was examined.
RESULTS 87 cases of retinal vascular occlusive disease (mean age 68.7 years) comprising 26 cases of retinal artery occlusion and 61 of retinal vein occlusion were compared with 87 controls (mean age 70.2 years). The TT genotype did not confer a significantly increased risk of retinal vascular occlusive disease. The mean tHcy level was significantly higher in the cases than in the controls (p<0.0001). Overall, and in both the cases and controls, the frequency of the TT genotype was higher in those with normal tHcy levels than in those with increased levels of tHcy. However, the TT genotype did not significantly alter the risk of increased tHcy levels in these patients.
CONCLUSIONS The TT genotype is not associated with an increased risk of retinal vascular occlusive disease or increased tHcy levels in this group of elderly patients. In older patients, nutritional rather than genetic factors may be more important in increasing tHcy levels, a known risk factor for retinal vascular occlusive disease.
- retinal vascular occlusive disease
- methylenetetrahydrofolate reductase (MTHFR) genotype