Methylenetetrahydrofolate reductase [MTHFR-677 and MTHFR-1298] genotypes and haplotypes and plasma homocysteine levels in patients with occlusive artery disease and deep venous thrombosis

• Autorzy: Spiroski I. , Kedev S. , Antov S. , Arsov T. , Krstevska M. , Dzhekova-Stojkova S. , Bosilkova G. , Kostovska S. , Trajkov D. , Petlichkovski A. , Strezova A. , Efinska-Mladenovska O. , Spiroski M.
• Języki publikacji: EN

Abstrakty

EN

The aim was to investigate different genotypes and haplotypes of methylenetetrahydrofolate reductase (MTHFR-677, -1298) and plasma concentration of total homocysteine (tHcy) in Macedonian patients with occlusive artery disease (OAD) and deep venous thrombosis (DVT). Investigated groups consists of 80 healthy, 74 patients with OAD, and 63 patients with DVT. Plasma tHcy was measured with Microplate Enzyme Immunoassay. Identification of MTHFRgenotypes and haplotypes was done with CVD StripAssay. The probability level (P-value) was evaluated by the Student’s t-test. Plasma concentration of tHcy in CC and CTgenotypes of MTHFR C677T was significantly increased in patients with OAD and in patients with DVT. Plasma concentration of tHcy in ACgenotype of MTHFR A1298C was increased in patients with OAD and in patients with DVT. Plasma concentration of tHcy was significantly increased in AA genotype of patients with OAD, but not in patients with DVT. We found a significant increase of plasma tHcy in patients with OAD in comparison with healthy respondents for normal: heterozygote (CC:AC), heterozy-gote:normal (CT:AA), and heterozygote: heterozygote (CT:AC) haplotypes. Plasma concentration of tHcy in patients with DVT in comparison with healthy respondents was significantly increased for normal:normal (CC:AA), normal heterozygote (CC:AC), and heterozygote: heterozygote (CT:AC) haplotypes. We conclude that MTHFR C677T and MTHFR A1289C genotypes and haplotypes are connected with tHcy plasma levels in Macedonian patients with OAD and DVT.

Słowa kluczowe

PL

methylenetetrahydrofolate reductase; cardiovascular disease; genotype; haplotype; plasma homocysteine level; patient; occlusive artery disease; venous thrombosis; deep venous thrombosis

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 2008
• Tom: 55
• Numer: 3
• Opis fizyczny: p.587-594,fig.,ref.

Twórcy

autor

Spiroski I.

• University 'Ss. Kiril and Metodij', 1109 Skopje, PO Box 60, Republic of Macedonia

autor

Kedev S.

autor

Antov S.

autor

Arsov T.

autor

Krstevska M.

autor

Dzhekova-Stojkova S.

autor

Bosilkova G.

autor

Kostovska S.

autor

Trajkov D.

autor

Petlichkovski A.

autor

Strezova A.

autor

Efinska-Mladenovska O.

autor

Spiroski M.

Bibliografia

• Ariyaratnam R, Casas JP, Whittaker J, Smeeth L, Hingorani AD, Sharma P (2007) Genetics of ischaemic stroke among persons of non-European descent: A meta-analysis of eight genes involving 32500 individuals. PLoS Med 4:e131.
• Bailey LB, Duhaney RL, Maneval DR, Kauwell GP, Quinlivan EP, Davis SR, Cuadras A, Hutson AD, Gregory JF 3rd (2002) Vitamin B-12 status is inversely associated with plasma homocysteine in young women with C677T and/or A1298C methylenetetrahydrofolate reductase polymorphisms. J Nutr 132:1872-1878.
• Bezemer ID, Doggen CJ, Vos HL, Rosendaal FR (2007) No association between the common MTHFR 677C-->T polymorphism and venous thrombosis: results from the MEGA study. Arch Intern Med 167:: 497-501.
• Cronin S, Furie KL, Kelly PJ (2005) Dose-related association of MTHFR677T allele with risk of ischemic stroke evidence from a cumulative meta-analysis. Stroke 36:1581-1587.
• Den Heijer M, Lewington S, Clarke R (2005) Homocysteine, MTHFR and risk of venous thrombosis: a meta-analysis of published epidemiological studies. J Thromb Haemost 3:292-399.
• den Heijer M, Rosendaal FR, Blom HJ, Gerrits WB, Bos GM (1998) Hyperhomocysteinemia and venous thrombosis: a meta-analysis. Thromb Haemost 80:874-877.
• Domagala TB, Adamek L, Nizankowska E, Sanak M, Szczeklik A (2002) Mutations C677T and A1298C of the 5,10-methylenetetrahydrofolate reductase gene and fasting plasma homocysteine levels are not associated with the increased risk of venous thromboembolic disease. Blood Coagul Fibrinolysis 13:423-431.
• Frantzen F, Faaren AL, Alfheim I, Nothei AK (1998) The enzyme conversion immunoassay for determining total homocysteine in plasma or serum. Clin Chem 44:311-316.
• Freitas AI, Mendonca I, Guerra G, Brion M, Reis RP, Carracedo A, Brehm A (2008) Methylenetetrahydrofolate reductase gene, homocysteine and coronary artery disease: The A1298C polymorphism does matter. Inferences from a case study (Madeira, Portugal). Thromb Res 122:648-56.
• Ghazouani L, Abboud N, Mtiraoui N, Zammiti W, Addad F, Amin H, Almawi WY, Mahjoub T (2008) Homocysteine and methylenetetrahydrofolate reductase C677T and A1298C polymorphisms in Tunisian patients with severe coronary artery disease. J Thromb Thrombolysis[Epub ahead of print].
• Goyette P, Sumner JS, Milos R, Duncan AMV, Rosenblatt DS, Matthews RG, Rozen R (1994) Human methylenetetrahydrofolate reductase: isolation of cDNA, mapping and mutation identification. Nature Genet 7:195-200.
• Goyette P, Pai A, Milos R, Frosst P, Tran P, Chen Z, Chan M, Rozen R (1998) Gene structure of human and mouse methylenetetrahydrofolate reductase (MTHFR). Mamm Genome 9:652-656.
• Hotoleanu C, Porojan-Iuga M, Rusu ML, Andercou A (2007) Hyperhomocysteinemia: clinical and therapeutical involvement in venous thrombosis. Rom J Intern Med 45:159-164.
• Keijzer MB, Borm GF, Blom HJ, Bos GM, Rosendaal FR, den Heijer M (2007) No interaction between factor V Leiden and hyperhomocysteinemia or MTHFR 677TT genotype in venous thrombosis. Results of a meta-analysis of published studies and a large case-only study. Thromb Haemost 97:32-37.
• Klerk M, Verhoef P, Clarke R, Blom HJ, Kok FJ, Schouten EG (2002) MTHFR Studies Collaboration Group: MTHFR 677C-T polymorphism and risk of coronary heart disease: a meta-analysis. JAMA 288:2023-2031.
• Kothekar MA (2007) Homocysteine in cardiovascular disease: a culprit or an innocent bystander? Indian J Med Sci 61:361-371.
• Krstevska M (2001) Total homocysteine levels in healthy pre- and postmenopausal women. Acta Pharm 51:225-231.
• Krstevska M, Dzhekova-Stojkova S, Bosilkova G (2001) Distribution of the total homocysteine values in female population. Jugoslav Med Biochem 20:207-211.
• Lancaster A, Nelson MP, Meyer D, Thomson G, Single RM (2003) PyPop: a software framework for population genomics: analyzing large-scale multi-locus genotype data. Pac Symp Biocomput 514-525.
• Lancaster AK, Single RM, Solberg OD, Nelson MP, Thomson G (2007) PyPop update - a software pipeline for large-scale multilocus population genomics. Tissue Antigens 69 (Suppl 1): 192-197.
• Lewis SJ, Ebrahim S, Smith GD (2005) Meta-analysis of MTHFR 677C-->T polymorphism and coronary heart disease: does totality of evidence support causal role for homocysteine and preventive potential of folate? BMJ doi:10.1136 331 1-6.
• McNulty H, Pentieva K, Hoey L, Ward M (2008) Homocysteine, B-vitamins and CVD. Proc Nutr Soc 67:232-237.
• Ogino S, Wilson RB (2003) Genotype and haplotype distributions of MTHFR677C>T and 1298A>C single nucleotide polymorphisms: a meta-analysis. J Hum Genet 48:1-7.
• Poduri A, Mukherjee D, Sud K, Kohli HS, Sakhuja V, Khullar M (2008) MTHFR A1298C polymorphism is associated with cardiovascular risk in end stage renal disease in North Indians. Mol Cell Biochem 308:43-50.
• Refsum H, Ueland PM (1998) Recent data are not in conflict with homocysteine as a cardiovascular risk factor. Curr Opin Lipidol 9:533-539.
• Salomon O, Rosenberg N, Zivelin A, Steinberg DM, Kornbrot N, Dardik R, Inbal A, Seligsohn U (2001) Methionine synthase A2756G and methylenetetrahydrofolate reductase A1298C polymorphisms are not risk factors for idiopathic venous thromboembolism. Hematol J 2:38-41.
• Sawula W, Banecka-Majkutewicz Z, Kadzinski L, Jakobkiewicz-Banecka J, Wegrzyn G, Nyka W, Banecki B (2008) Improved HPLC method for total plasma homocysteine detection and quantification. Acta Biochim Polon 55:119-125.
• Sazci A, Ergul E, Tuncer N, Akpinar G, Kara I (2006) Methylenetetrahydrofolate reductase gene polymorphisms are associated with ischemic and hemorrhagic stroke: Dual effect of MTHFR polymorphisms C677T and A1298C. Brain Res Bull 71:45-50.
• Single RM, Meyer D, Mack SJ, Lancaster A, Erlich HA, Thomson G (2007) 14th International HLA and Immunogenetics Workshop: report of progress in methodology, data collection, and analyses. Tissue Antigens 69(Suppl 1): 185-187.
• Souto JC, Blanco-Vaca F, Soria JM, Buil A, Almasy L, Ordonez-Llanos J, Martin-Campos JM, Lathrop M, Stone W, Blangero J, Fontcuberta J (2005) A genomewide exploration suggests a new candidate gene at chromosome 11q23 as the major determinant of plasma homocysteine levels: results from the GAIT Project. Am J Hum Genet 76:925-933.
• Spiroski M, Arsov T, Petlichkovski A, Strezova A, Trajkov D, Efinska-Mladenovska O, Zaharieva E (2005) Case Study: Macedonian Human DNA Bank (hDNAMKD) as a source for public health genetics. In: Health Determinants in the Scope of New Public Health,Georgieva L, Burazeri G, ed, pp 33-44. Hans Jacobs Company: Sofia.
• Spiroski I, Kedev S, Antov S, Arsov T, Krstevska M, Dzhekova-Stojkova S, Kostovska S, Trajkov D, Petlichkovski A, Strezova A, Efinska-Mladenovska O, Spiroski M (2008) Association of methylenetetrahydrofolate reductase (MTHFR-677 and MTHFR-1298) genetic polymorphisms with occlusive artery disease and deep venous thrombosis in Macedonians. Croat Med J 49:39-49.
• Strandhagen E, Zetterberg H, Aires N, Palmer M, Rymo L, Blennow K, Landaas S, Thelle DS (2004) The methylenetetrahydrofolate reductase C677T polymorphism is a major determinant of coffee-induced increase of plasma homocysteine: a randomized placebo controlled study. Int J Mol Med 13:811-815.
• Towner P (1995) Purification of DNA. Essential Molecular Biology. Brown TA ed, pp 47-54. Oxford University Press, Oxford.
• Tunbridge EM, Harrison PJ, Warden DR, Johnston C, Refsum H, Smith AD (2008) Polymorphisms in the catechol-O-methyltransferase (COMT) gene influence plasma total homocysteine levels. Am J Med Genet B Neuropsychiatr Genet 147B:996-9.
• van der Linden IJ, den Heijer M, Afman LA, Gellekink H, Vermeulen SH, Kluijtmans LA, Blom HJ (2006) The methionine synthase reductase 66A>G polymorphism is a maternal risk factor for spina bifida. J Mol Med 84:1047-1054.
• Wald DS, Law M, Morris JK (2002) Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. BMJ 325:1202.
• Yang QH, Botto LD, Gallagher M, Friedman JM, Sanders CL, Koontz D, Nikolova S, Erickson JD, Steinberg K (2008) Prevalence and effects of gene-gene and gene-nutrient interactions on serum folate and serum total homocysteine concentrations in the United States: findings from the third National Health and Nutrition Examination Survey DNA Bank. Am J Clin Nutr 88:232-246.
• Zak I, Niemiec P, Sarecka B, Balcerzyk A, Ciemniewski Z, Rudowska E, Dylag S (2003) Carrier-state of D allele in ACE gene insertion/deletion polymorphism is associated with coronary artery disease, in contrast to the C677-->T transition in the MTHFR gene. Acta Biochim Polon 50:527-534.