Hyperhomocysteinemia and Related Genetic Polymorphisms Correlate with Ulcerative Colitis in Southeast China
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Increased levels of homocysteine are found systemically and in intestinal mucosa of patients with inflammatory bowel disease, and, specifically, in ulcerative colitis (UC). However, there are controversial reports regarding the factors contributing to increased levels of homocysteine in UC. Furthermore, little information is available regarding the relationship between hyperhomocysteinemia (HHcy), vitamin status, and genetic polymorphisms of homocysteine-related enzymes in these patients. This study examined four functional polymorphisms linked to homocysteine metabolism (MTHFR C677T and A1298C, MTR A2756G and MTRR A66G), and evaluated plasma levels of homocysteine, folate, and vitamin B12 in 310 consecutive patients with UC and 936 age- and sex-matched healthy controls from southeast China. The variant allele and genotypic frequencies in MTHFR A1298C, MTR A2756G and MTRR A66G genes were significantly higher in patients with UC compared to healthy controls. Further, HHcy and low levels of folate and vitamin B12 were more frequent in patients with UC. The MTR 2756G allele, extent of the disease, and gender were the independent determinants of HHcy in these patients. These findings suggest that genetic and nutritional factors have a synergetic effect on HHcy in patients with UC. In conclusion, our data highlight a prevention strategy for moderation of HHcy and supplementation with folate and vitamine B12 in patients with UC from Southeast China.
KeywordsUlcerative colitis Hyperhomocysteinemia Genetic polymorphism Folate Vitamin B12
This study was supported by grants from Ministry of Health of China for Welfare Projects (200802156), Clinical Research Center for Intestinal & Colorectal Diseases of Hubei Province (2008BCC002), and Hubei Provincial Science & Technology Fund for International Cooperation (2007CA003).
- 3.Chen, M., Peyrin-Biroulet, L., Xia, B., Gueant-Rodriguez, R. M., Bronowicki, J. P., Bigard, M. A., et al. (2008). Methionine synthase A2756G polymorphism may predict ulcerative colitis and methylenetetrahydrofolate reductase C677T pancolitis, in Central China. BMC Medical Genetics, 9, 78.PubMedCrossRefGoogle Scholar
- 10.Gabriel, H. E., Crott, J. W., Ghandour, H., Dallal, G. E., Choi, S. W., Keyes, M. K., et al. (2006). Chronic cigarette smoking is associated with diminished folate status, altered folate form distribution, and increased genetic damage in the buccal mucosa of healthy adults. American Journal of Clinical Nutrition, 83, 835–841.PubMedGoogle Scholar
- 12.Laraqui, A., Allami, A., Carrie, A., Raisonnier, A., Coiffard, A. S., Benkouka, F., et al. (2007). Relation between plasma homocysteine, gene polymorphisms of homocysteine metabolism-related enzymes, and angiographically proven coronary artery disease. European Journal of Internal Medicine, 18, 474–483.PubMedCrossRefGoogle Scholar
- 13.Leclerc, D., Campeau, E., Goyette, P., Adjalla, C. E., Christensen, B., Ross, M., et al. (1996). Human methionine synthase: cDNA cloning and identification of mutations in patients of the cblG complementation group of folate/cobalamin disorders. Human Molecular Genetics, 5, 1867–1874.PubMedCrossRefGoogle Scholar
- 14.Mahmood, A., Needham, J., Prosser, J., Mainwaring, J., Trebble, T., Mahy, G., et al. (2005). Prevalence of hyperhomocysteinaemia, activated protein C resistance and prothrombin gene mutation in inflammatory bowel disease. European Journal of Gastroenterology and Hepatology, 17, 739–744.PubMedCrossRefGoogle Scholar
- 16.Morgenstern, I., Raijmakers, M. T., Peters, W. H., Hoensch, H., & Kirch, W. (2003). Homocysteine, cysteine, and glutathione in human colonic mucosa: Elevated levels of homocysteine in patients with inflammatory bowel disease. Digestive Diseases and Sciences, 48, 2083–2090.PubMedCrossRefGoogle Scholar
- 20.Papa, A., De Stefano, V., Danese, S., Chiusolo, P., Persichilli, S., Casorelli, I., et al. (2001). Hyperhomocysteinemia and prevalence of polymorphisms of homocysteine metabolism-related enzymes in patients with inflammatory bowel disease. American Journal of Gastroenterology, 96, 2677–2682.PubMedCrossRefGoogle Scholar
- 21.Peyrin-Biroulet, L., Rodriguez-Gueant, R. M., Chamaillard, M., Desreumaux, P., Xia, B., Bronowicki, J. P., et al. (2007). Vascular and cellular stress in inflammatory bowel disease: revisiting the role of homocysteine. American Journal of Gastroenterology, 102, 1108–1115.PubMedCrossRefGoogle Scholar