BACKGROUND: The purpose of this study was to investigate plasma homocysteine levels and polymorphisms in genes encoding enzymes in the metabolic pathway of homocysteine in association with primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (PXFG).METHODS: A total of 156 glaucoma patients (76 with POAG and 80 with PXFG) and 135 controls matched for age and sex were enrolled in this study. Plasma homocysteine levels were measured using a commercially available enzyme-linked immunosorbent assay kit. DNA was extracted from peripheral blood leukocytes and real-time polymerase chain reaction was performed for genotyping of the samples. Patients were genotyped using predesigned TaqMan(®) single nucleotide polymorphism genotyping assays for two exon variations (rs1801131, rs1801133) in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene and one intron variation (rs8006686) in the methylenetetrahydrofolate dehydrogenase (MTHFD1) gene.RESULTS: Homocysteine levels were slightly higher in the patient group (POAG and PXFG) compared with controls, but the difference did not reach statistical significance. The minor alleles of the MTHFR single nucleotide polymorphisms showed a protective effect for POAG and showed an increased risk for PXFG, but none of these associations reached statistical significance (P>0.05). The minor allele of MTHFD1 rs8006686 showed a trend for increased risk of both POAG and PXFG (P>0.05). No statistically significant interaction was seen between the genetic variants and homocysteine levels (P>0.05).CONCLUSION: Our results show that neither the examined single nucleotide polymorphisms from genes involved in the pathway of homocysteine metabolism nor the measured homocysteine levels were associated with POAG or PXFG in our study cohort.