Homocysteine, methylenetetrahydrofolate reductase C677T polymorphism, and risk of retinal vein occlusion: a meta-analysis.
OBJECTIVE
To assess the role of plasma total homocysteine (tHcy) concentrations and homozygosity for the thermolabile variant of the methylenetetrahydrofolate reductase (MTHFR) C677T gene as risk factors for retinal vascular occlusive disease.


METHODS
Retinal vein occlusion (RVO) is an important cause of vision loss. Early meta-analyses showed that tHcy was associated with an increased risk of RVO, but a significant number of new studies have been published.


METHODS
RVO patients and controls.


METHODS
Data sources included MEDLINE, Web of Science, and PubMed searches and searching reference lists of relevant articles and reviews. Reviewers searched the databases, selected the studies, and then extracted data. Results were pooled quantitatively using meta-analytic methods.


METHODS
tHcy concentrations and MTHFR genotype.


RESULTS
There were 25 case-control studies for tHcy (1533 cases and 1708 controls) and 18 case-control studies for MTHFR (1082 cases and 4706 controls). The mean tHcy was on average 2.8 micromol/L (95% confidence interval [CI], 1.8-3.7) greater in the RVO cases compared with controls, but there was evidence of between-study heterogeneity (P<0.001, I(2) = 93%). There was funnel plot asymmetry suggesting publication bias. There was no evidence of association between homozygosity for the MTHFR C677T genotype and RVO (odds ratio [OR] 1.20; 95% CI, 0.84-1.71), but again marked heterogeneity (P = 0.004, I(2) = 53%) was observed.


CONCLUSIONS
There was some evidence that elevated tHcy was associated with RVO, but not homozygosity for the MTHFR C677T genotype. Both analyses should be interpreted cautiously because of marked heterogeneity between the study estimates and possible effect of publication bias on the tHcy findings.


BACKGROUND
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
McGimpsey
Stuart J
SJ
Directorate of Ophthalmology, The Royal Victoria Hospital, The Belfast Health and Social Care Trust, Grosvenor Road, Belfast, Ireland.
Woodside
Jayne V
JV
Cardwell
Chris
C
Cahill
Mark
M
Chakravarthy
Usha
U
D016208:Databases, Factual; D005838:Genotype; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012170:Retinal Vein Occlusion / Q000097:blood* / Q000235:genetics*; D012307:Risk Factors
D006710:Homocysteine; D042965:Methylenetetrahydrofolate Reductase (NADPH2)