Prevalence Of The Mutation C677 → T In The Methylene Tetrahydrofolate Reductase Gene Among Distinct Ethnic Groups In Brazil

Abstract

Vascular disease is a serious public health problem in the industrialized world, and is a frequent cause of death among the adult population of Brazil. Mild hyperhomocysteinemia has been identified as a risk factor for arterial disease, venous thrombosis, and neural tube defects. Individuals homozygous for the thermolabile variant of methylenetetrahydrofolate reductase (MTHFR-T) are found in 5-15% of the general population and have significantly elevated plasma homocysteine levels which represent one of the genetic risk factors for vascular diseases. We have analyzed the prevalence of individuals homozygous for the MTHFR-T in 327 subjects representing the three distinct ethnic groups in Brazil. The prevalence of homozygotes for the mutated allele MTHFR-T was high among persons of Caucasian descent (10%) and considerably lower among Black (1.45%) and Indians persons populations (1.2%). These data suggest that screening for the MTHFR-T allele should help in identifying individuals with a high risk of vascular disease among populations with a heterogeneous background.784332335Arruda, V.R., Von Zuben, P.M., Soares, M.C.P., Menezes, R., Annichino-Bizzacchi, J.M., Costa, F.F., Very low incidence of Arg506 → Gln mutation in the factor V gene among the Amazonian Indians and the Brazilian black population (1996) Thromb Haemost, 75, pp. 860-861Arruda, V.R., Von Zuben, P.M., Annichino-Bizzacchi, J.M., Costa, F.F., The mutation Ala677 → Val in the methylenetetrahydrofolate reductase gene: A risk factor for premature arterial disease and venous thrombosis (1997) Thromb Haemost, 77, pp. 818-821Black, F.L., Salzano, F.M., Layrisse, Z., Franco, M.H.L.P., Harris, N.S., Weimer, T.A., Restriction and persistence of polymorphisms of HLA and other blood genetic traits in the Parakanā Indians of Brazil (1980) Am J Phys Anthr, 52, pp. 119-132Boushey, C.J., Beresford, S.A.A., Omenn, G.S., Motulsky, A.G., A quantitative assessment of plasma homocysteine as a risk factor for vascular disease (1995) JAMA, 274, pp. 1049-1057Cavalli-Sforza, L.L., Piazza, A., Menozzi, P., Montain, J., Reconstruction of human evolution: Bringing together genetic, archaelogical and linguistic data (1988) Proc Natl Acad Sci USA, 85, pp. 6002-6006Clarke, R., Daly, L., Robinson, K., Hyperhomocysteinemia: An independent risk factor for vascular disease (1991) N Engl J Med, 324, pp. 1149-1155Curtin, P.D., (1969) The Slave Atlantic Trade: A Census, , Milwaukee: University of Wisconsin PressDean, A.G., Dean, J.A., Coulombier, D., Brendel, K.A., Smith, D.C., Burton, A.H., Dicker, R.C., Arner, T.G., (1994) Epi Info, Version 6: A Word Processing, Database, and Statistics Program for Epidemiology on Microcomputers, , Atlanta: Center for Disease Control and PreventionDen Heijer, M., Koster, T., Blom, H.J., Bos, G.M.J., Briet, E., Reitsma, P.H., Vandenbroucke, J.P., Rosendaal, F.R., Hyperhomocysteinemia as a risk factor for deep-vein thrombosis (1996) N Engl J Med, 334, pp. 759-762Duncan, B.B., Schmidt, M.I., Polanczyk, C.A., Mengue, S.S., High mortality rates in Brazilian adult populations-an international comparison (1992) Rev Ass Med Brasil, 38, pp. 138-144Engbersen, A.M.T., Franken, D.G., Boers, G.H.J., Stevens, E.M.B., Trijbels, F.J.M., Blom, H.J., Thermolabile 5,10-methylenetetrahydrofolate reducttase as a cause of mild hypermocysteinemia (1995) Am J Hum Genet, 56, pp. 142-150Falcon, C.R., Cattaneo, M., Panzeri, D., Martinelli, I., Mannucci, P.M., High prevalence of hyperhomocyst(e)inemia in patients with juvenile venous thrombosis (1994) Arterioscler Thromb, 14, pp. 1080-1083Franken, D.G., Boers, G.H.J., Blom, H.J., Trijbels, J.M.F., Kloppernborg, P.W.C., Treatment of mild hyperhomocysteinemia in vascular disease patients (1994) Arterioscler Thromb, 14, pp. 465-470Froost, P., Blom, H.J., Milos, R., Goyette, P., Sheppard, C.A., Matthews, R.G., Boers, G.H.J., Rozen, R., A candidate genetic risk factor for vascular disease: A common mutation in methylenetetrahydrofolate reductase (1995) Nature Genet, 10, pp. 111-113Gallagher, P.M., Meleady, R., Shields, D.C., Tan, K.S., McMaster, D., Rozen, R., Evans, A., Whitehead, A.S.D., Homocysteine and risk of premature coronary heart disease (1996) Circulation, 94, pp. 2154-2158Kang, S.S., Wong, P.W.K., Susmano, A., Sora, J., Norusis, M., Ruggie, N., Thermolabile methylenetetrahydrofolate reductase: An inherited risk factor for coronary artery disease (1991) Am J Hum Genet, 48, pp. 536-545Kluijtmans, L.A.J., Van Den Heuvel, L.P.W.J., Boers, G.H.J., Frosst, P., Stevens, E.M.B., Van Oost, B.A., Den Heijer, M., Rozen, R.I., Molecular genetic analysis in mild hyperhomocysteinemiaa common mutation in methylenetetrahydrofolate reductase gene is a genetic risk factor for cardiovascular disease (1996) Am J Human Genet, 58, pp. 35-41McCully, K.S., Vascular pathology of homocysteinemia (1969) Am J Pathol, 56, pp. 111-128McCully, K.S., Homocysteine and vascular disease (1996) Nature Medicine, 2, pp. 386-389Millar, S.A., Dykes, D.D., Polesky, H.F., A simple salting out procedure for extracting DNA from nucleated cell (1988) Nucleic Acids Res, 16, p. 1215Motulsky, A.G., Nutritional ecogenetics: Homocysteine-related arteriosclerotic vascular disease, neural tube defects, and folic acid (1996) Am J Hum Genet, 58, pp. 17-20Ou, C.Y., Stevenson, R.E., Brown, V.K., Schwartz, C.E., Allen, W.P., Khoury, M.J., Rozen, R., Adams Jr., M.J., 5,10 Methylenetetrahydofolate reductase genetic polymorphism as a risk factor for neural tube defects (1996) Am J Med Genet, 63, pp. 610-614Rees, D.C., Cox, M., Clegg, J.B., World distribution of factor V Leiden (1995) Lancet, 346, pp. 1133-1134Saiki, R.K., Gelfand, D.H., Stoffel, S., Scharf, S.J., Higuchi, R., Horn, G.T., Mullis, K.B., Erlich, H.A., Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase (1988) Science, 239, pp. 487-491Stevenson, R.E., Schwartz, C.E., Du, Y.-Z., Adams Jr., M.J., Differences in methylelenetetrahydrofolate reductase geneotype frequencies, between whites and blacks (1997) Am J Hum Genet, 60, pp. 229-230Ubbink, J.B., Vermaak, W.J.H., Delport, R., Van Der Merwe, A., Becker, P.J., Potgieter, H., Effective homocysteine metabolism may protect South African blacks against coronary heart disease (1995) Am J Clin Nutr, 62, pp. 802-808Recommendation for the use of folic acid to reduce the number of cases of spina bifida and other neural tube defects (1992) MMWR, 41, pp. 1-7Van Der Put, N.M.J., Steegers-Theunissen, R.P.M., Froost, P., Trijbels, F.J.M., Eskes, T.K.A.B., Van Den Heuvel, L.P., Mariman, E.C.M., Blom, H.J., Mutated methylenetetrahydofolate reductase as a risk factor for spina bifida (1995) Lancet, 346, pp. 1070-1071Verhoef, P., Stampfer, M.J., Buring, J.E., Gaziano, J.M., Allen, R.H., Stabler, S.P., Reynolds, R.D., Willett, W.C., Homocysteine metabolism and risk of myocardial infarction: Relation with vitamin B6, B12, and folate (1996) Am J Epidemiol, 143, pp. 845-859Diet Nutrition, and the Prevention of Chronic Diseases (1990) WHO Technical Report Series No. 797, , Report of a WHO Study GroupCardiovascular Disease Risk Factor: New Areas for Research (1994) WHO Technical Report Series, No. 841, , Report of a WHO Scientific GroupZivelin, A., Griffin, J.H., Xu, X., Pabinger, I., Samama, M., Conard, J., Brenner, B., Seligsohn, U., A single genetic origin for a common caucasian risk factor for venous thrombosis (1997) Blood, 89, pp. 397-40