The Relationship Among Homocysteine, Folate And MTHFRC677T Mutation In Central Retinal Vein Occlusion: A Case-control Study In The Chinese Population

Background: Central retinal vein occlusion (CRVO) is a common cause of visual loss and currently there is no effective and reliable treatment. CRVO has multiple risk factors, but pathogenesis and risk factors are still poorly understood. Homocysteine is an intermediate amino acid product in the metabolism of sulfur amino acids, in which the essential amino acid methionine is catabolized to produce cysteine. Homocysteine may be metabolized further either through irreversible transsulfuration to cystathionine and cysteine or remethylated to form methionine again. Recent studies suggest that elevated levels of plasma homocysteine may be an independent risk factor for venous thrombosis and cardiovascular disease, and also found the MTHFRC677T mutation causes an approximately 50% decrease in enzyme activity from the normal level and it may be associated with moderately elevated plasma homocysteine levels, especially in the presence of suboptimal folate availability. Despite the fact that a number of studies on the relationship between Hyperhomocysteinemia and CRVO, a venous thrombosis disease, have been conducted in recent years, and MTHFR C677T mutation has been investigated in patients with CRVO, the conclusions still remain controversial.Objective: To investigate the association of both hyperhomocysteinemia, low plasma folate and MTHFRC677T mutation with CRVO in Chinese population.Materials and methods: A matched case-control study was conducted between July 2004 and May 2005. The study cohort consisted of 64 individuals that had been diagnosed with CRVO and 64 healthy controls (matched for age, gender, hypertension, smoking, and drinking habits). None of the cases or controls had a history of diabetes, glaucoma, medication or any other vascular events that might influence plasma homocysteine levels. A cross-sectional analysis among the 64 cases was performed to compare the prevalence of compare the prevalence of low plasma folate Hyperhomocysteinemia, and MTHFRC677T mutation among subjects with and without ischemia and subjects aged above 45 and below 45 years. Plasma homocysteine level was measured by means of high-performance liquid chromatography and plasma folate concentration by Radioimmunoassay. MTHFRC677T mutation was determined by the template- directed dye-terminator incorporation with fluorescence polarization (TDI-FP) method.Results: The CRVO patients had a significantly higher homocysteine level (13.83±1.71μmol/l) than the normal controls (8.05±0.58μmol/l, P=0.003). The plasma folate levels were significantly lower in CRVO patients than in controls (5.62±0.39 ng/dl vs 7.23±0.60ng/dl, P=0.032). A 1μmol/l increase of plasma homocysteine level was associated with an odds ratio of 1.368. Hyperhomo- cysteinemia was defined as a homocysteine level of >14.97μmol/l and was seen in 11 patients in the ischemic group, significantly more often than in the non-ischemic group (5 patients, P=0.030). The prevalence of the MTHFR677TT genotype did not significantly differ between patients and controls. However, 10 (34.5%) MTHFR677TT genotype was found in the ischemic group but only 4 (14.3%) in the nonischemic group (P=0.026). And we found that 6 MTHFR677TT genotype patients who have hyperhomocysteinemia in the ischemic group but only 2 in the nonischemic group (P=0.016).Conclusions: The results suggest that hyperhomocysteinemia and low plasma folate are independent risk factors for CRVO and are associated with the development of CRVO in the Chinese population. MTHFRC677T mutation is associated with hyperhomocysteinemia in the ischemic CRVO in the Chinese population. It may contribute to hyperhomocysteinemia and associate with the development of CRVO.