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Hyperhomocysteinemia and low plasma folate as risk factors for central retinal vein occlusion: a case–control study in a Chinese population

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To determine whether hyperhomocysteinemia and low plasma folate are risk factors for central retinal vein occlusion (CRVO) in the Chinese population.


A matched case–control study was conducted between July 2004 and May 2005. The study cohort consisted of 64 individuals that had been diagnosed to have CRVO and 64 normal 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 minimize the influence on plasma homocysteine levels. A cross-sectional analysis among the 64 cases was performed to compare the prevalence of hyperhomocysteinemia and low plasma folate among subjects with and without ischemia and subjects with age above 45 and below 45 years. Plasma homocysteine level was measured by means of high-performance liquid chromatography and plasma folate concentration by radioimmunoassay.


The CRVO patients had a significantly higher homocysteine level (13.83±1.71 μmol/l) than the normal controls (8.05±0.58 μmol/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±0.60 ng/dl; p=0.032). A 1 μmol/l increase of plasma homocysteine level was associated with an odds ratio of 1.368. Hyperhomocysteinemia was defined as a homocysteine level of >14.97 μmol/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 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.

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  1. Abu El-Asrar AM, Abdel Gader AG, Al-Amro SA, Al-Attas OS (2002) Hyperhomocysteinemia and retinal vascular occlusion disease. Eur J Ophthalmol 12:495–500

    PubMed  CAS  Google Scholar 

  2. Boyd S, Owens D, Gin T, Bunce K, Sherafat H, Perry D, Hykin PG (2001) Plasma homocysteine, methylenetetrahydrofolate reeducates C677T and factor II G20210A polymorphisms, factor VIII, and VWF in central retinal vein occlusion. Br J Ophthalmol 85:1313–1315

    Article  PubMed  CAS  Google Scholar 

  3. Cabezas-Leon MM, Garcia-Montero MR, Morente-Matas P(2003) Hyperhomocysteinemia as a risk factor for central retinal vein thrombosis in a young patient. Rev Neurol 37:441–443

    PubMed  CAS  Google Scholar 

  4. De Franchis R, Mancini FP, D’Angelo A, Sebastio G, Fermo I, de Stefano V, Margaglione M, Mazzola G, di Minno G, Andria G (1996) Elevated total plasma homocysteine and 677C3T mutation of the 5, 10-methylenetetrahydrofolate reductase gene in thrombotic vascular disease. Am J Hum Genet 59:262–264

    PubMed  Google Scholar 

  5. Engbersen AMT, Franken DG, Boers GHJ, Stevens EMB, Trijbels FJM, Blom HK (1995) Thermolabile 5,10-methylenetetrahydrofolate reductase as a cause for mild hyperhomocysteinemia. Am J Hum Genet 56:142–150

    PubMed  CAS  Google Scholar 

  6. Graham IM, Daly LE, Refsum HM, Robinson K, Brattstrom LE, Ueland PM (1997) Plasma homocysteine as a risk factor for vascular disease. The European Concerted Action Project. JAMA 277:1775–1781

    Article  PubMed  CAS  Google Scholar 

  7. Hak AE, Polderman KH, Westendorp I, Jakobs C, Hofman A, Witteman JCM, Stehouwer CD (2000) Increased plasma homocysteine after menopause. Atherosclerosis 149:163–168

    Article  PubMed  CAS  Google Scholar 

  8. Hayreh SS, Zimmerman MB, Podhajsky P (2002) Hematological abnormalities associated with various types of retinal vein occlusion. Graefes Arch Clin Exp Ophthalmol 240:180–196

    Article  PubMed  Google Scholar 

  9. Henning BF, Riezler RR, Tepel M, Langer K, Raidt H, Graefe U, Zidek W (1999) Evidence of altered homocysteine metabolism in chronic renal failure. Nephron 83:314–322

    Article  PubMed  CAS  Google Scholar 

  10. Hoogeveen EK, Kostense PJ, Beks PJ, Mackaay AJC, Jakobs C, Bouter LM, Heine RJ, Stehouwer CD (1998) Hyperhomocysteinemia is associated with an increased risk of cardiovascular disease, especially in non-insulin dependent diabetes mellitus: a population based study. Arterioscler Thromb Vasc Biol 18:133–138

    PubMed  CAS  Google Scholar 

  11. Larsson J, Hultberg B, Hillarp A (2000) Hyperhomocysteinemia and the MTHFR C677T mutation in central retinal vein occlusion. Acta Ophthalmol Scand 78:340–343

    Article  PubMed  CAS  Google Scholar 

  12. Malinow MR, Nieto FJ, Kruger WD, Duell PB, Hess DL, Gluckman RA, Block PC, Holzgang CR, Anderson PH, Seltzer D, Upson B, Lin QR (1997) The effects of folic acid supplementation on plasma total homocysteine are modulated by multivitamin use and methylenetetrahydrofolate reductase genotypes. Arterioscler Thromb Vasc Biol 17:1157–1162

    PubMed  CAS  Google Scholar 

  13. Malinow MR, Nieto FJ, Szklo M, Chambless LE, Bond G (1993) Carotid artery intimal-medial wall thickening and plasma homocysteine in asymptomatic adults. The Atherosclerosis Risk in Communities Study. Circulation 87:1107–1113

    PubMed  CAS  Google Scholar 

  14. Ray JG (1998) Meta–analysis of hyperhomocysteinemia as a risk factor for venous thromboembolic disease. Arch Intern Med 158:2101–2106

    Article  PubMed  CAS  Google Scholar 

  15. Refsum H, Ueland PM, Nygard O, Vollset SE (1998) Homocysteine and cardiovascular disease. Annu Rev Med 49:31–62

    Article  PubMed  CAS  Google Scholar 

  16. Weger M, Stanger O, Deutschmann H, Temmel W, Renner W, Schmut O, Quehenberge F, Semmelrock J, Haas A (2002) Hyperhomocyst(e)inemia, but not methylenetetrahydrofolate reductase C677T mutation, as a risk factor in branch retinal vein occlusion. Ophthalmology 109:1105–1109

    Article  PubMed  Google Scholar 

  17. Yildirim C, Yaylali V, Tatlipinar S, Kaptanoglu B, Akpinar S (2004) Hyperhomocysteinemia: a risk factor for retinal vein occlusion. Ophthalmologica 218:102–106

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Yu–Sheng Wang.

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Gao, W., Wang, Y., Zhang, P. et al. Hyperhomocysteinemia and low plasma folate as risk factors for central retinal vein occlusion: a case–control study in a Chinese population. Graefe's Arch Clin Exp Ophthalmo 244, 1246–1249 (2006).

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