Clinical Implications of Methylenetetrahydrofolate Reductase Mutations and Plasma Homocysteine Levels in Patients with Thromboembolic Occlusion

PURPOSE: Hyperhomocysteinemia has been identified as an independent risk factor in arterial and venous thrombosis. Mutations in genes encoding methylenetetrahydrofolate reductase (MTHFR), involved in the metabolism of homocysteine, may account for reduced enzyme activity and elevated plasma homocysteine levels. In this study, we investigated the interrelation of MTHFR C677T genotype and level of homocysteine in patients with arterial and venous thrombosis. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 146 patients who were diagnosed as having arterial and venous thrombosis. We excluded patients diagnosed with atrial fibrillation. We examined routinely the plasma concentration of total homocysteine level and MTHFR C677T polymorphism for evaluation of thrombotic tendency in all patients. Screening processes of MTHFR C677T polymorphism were performed by real-time polymerase chain reaction. RESULTS: Investigated groups consisted of thrombotic arterial occlusion in 48 patients and venous occlusion in 63 patients. The distribution of the three genotypes was as follows: homozygous normal (CC) genotype in 29 (26.1%), heterozygous (CT) genotype in 57 (51.4%), and homozygous mutant (TT) genotype in 25 (22.5%) patients. There were no significant differences among individuals between each genotype group for baseline characteristics. Plasma concentration of homocysteine in patients with the TT genotype was significantly increased compared to the CC genotype (P<0.05). CONCLUSION: We observed a significant interaction between TT genotypes and homocysteine levels in our results. The results might reflect the complex interaction between candidate genes and external factors responsible for thrombosis.