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Objective To investigate the association between the methylenetetrahydrofolate reductase gene C677T (MTHFR C677T) polymorphism and diabetic retinopathy (DR).Methods A total of 6971 subjects including 2707 DR patients and 4264 controls from 23 studies were enrolled in the study.A random-effects model was applied to estimate the overall effects and the stratified effects of the MTHFR C677T polymorphism on the risk of DR,and study quality was also assessed.Results Strong associations were observed between the MTHFR C677T polymorphism and DR.The carries of MTHFR C677T were more likely to be found in the DR group in relative to the healthy control group with odds ratio 1.68,2.55,and 2.31 respectively in allele contrast model (T vs.C,95％CI:1.29-2.18,P＜0.001,I2=78.4％),homozygous model (TT vs.CC,95％CI:1.70-3.83,P=0.008,I2=54.4％) and dominant model (TT+CT vs.CC,95％CI:1.62-3.29,P＜0.001,I2=74.7％).This assodation can also be found in contrast to the Ncd (non-complicated diabetic mellitus) group (allele contrast,OR=1.50,95％CI:1.07-2.11,P=0.032,I2=62.1％;homozygous,OR=2.39,95％CI:1.06-5.38,P=0.017,I2=66.7％;dominant,0R=1.59,95％CI:0.97-2.62,P=0.056,I2=56.5％).For the heterozygous model (CT vs.CC),the association was significant in contrast to the healthy control group (OR=1.46,95％CI:1.64-3.69,P=0,I2=77.3％),while in contrast to the Ncd control group the association was not statistically meaningful (OR=1.38,95％CI:0.87-2.18,P=0.131,I2=43.7％).For the recessive model,1.92-fold increased risk was found only in contrast to the Ncd control group (95％CI:1.07-3.43,P=0.064,I2=55.0％).There was no significant association found in the models in contrast to the DM control group.Conclusion In this meta-analysis,we found an association between the MTHFR C677T polymorphism and DR,especially in contrast to the Ncd control group.Further studies are required to establish more definite relationship.