title: Thermolabile MTHFR genotype and retinal vascular occlusive disease.
abstract: 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.
authors.affiliation: The Research Foundation, The Royal Victoria Eye and Ear Hospital, Dublin 2, Ireland. mark.cahill@joslin,harvard.edu
authors.forename: M
authors.initials: M
authors.lastname: Cahill
authors.forename: M
authors.initials: M
authors.lastname: Karabatzaki
authors.forename: C
authors.initials: C
authors.lastname: Donoghue
authors.forename: R
authors.initials: R
authors.lastname: Meleady
authors.forename: L A
authors.initials: LA
authors.lastname: Mynett-Johnson
authors.forename: D
authors.initials: D
authors.lastname: Mooney
authors.forename: I M
authors.initials: IM
authors.lastname: Graham
authors.forename: A S
authors.initials: AS
authors.lastname: Whitehead
authors.forename: D C
authors.initials: DC
authors.lastname: Shields
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006710:Homocysteine / Q000097:blood*; D006358:Hot Temperature; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D017354:Point Mutation; D015356:Retinal Artery Occlusion / Q000097:blood / Q000235:genetics*; D012170:Retinal Vein Occlusion / Q000097:blood / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D006710:Homocysteine; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)