MTHFR C677T genotype and cardiovascular risk in a general population without mandatory folic acid fortification

European Journal of Nutrition

Volumn 53, Issue 7, 2014, Pages 1549-1559

  Husemoen, Lise Lotte N ^a   Skaaby, Tea ^a   Jørgensen, Torben ^a,b   Thuesen, Betina H ^a   Fenger, Mogens ^c   Grarup, Niels ^d   Sandholt, Camilla H ^d   Hansen, Torben ^d,e   Pedersen, Oluf ^b,d,f,g   Linneberg, Allan ^a,b  

^a GLOSTRUP UNIVERSITY HOSPITAL   (Denmark)

^b UNIVERSITY OF COPENHAGEN   (Denmark)

^c HVIDOVRE HOSPITAL   (Denmark)

^d Capital Region   (Denmark)

^e UNIVERSITY OF SOUTHERN DENMARK   (Denmark)

^f AARHUS UNIVERSITY   (Denmark)

^g HAGEDORN RESEARCH INSTITUTE   (Denmark)

Author keywords

B12; Cardiovascular disease; Folate; Homocysteine; MTHFR; rs1801133

Indexed keywords

ANTIHYPERTENSIVE AGENT; ANTILIPEMIC AGENT; CYANOCOBALAMIN; FOLIC ACID; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; HOMOCYSTEINE; PROTEIN; PROTEIN MTHFR C677T; TRIACYLGLYCEROL; UNCLASSIFIED DRUG; LOW DENSITY LIPOPROTEIN CHOLESTEROL; METHYLENETETRAHYDROFOLATE REDUCTASE (NADPH2); MTHFR PROTEIN, HUMAN;

ADOLESCENT; ADULT; AGED; ARTICLE; ASSOCIATION; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; CEREBROVASCULAR ACCIDENT; DENMARK; DIASTOLIC BLOOD PRESSURE; DYSLIPIDEMIA; FEMALE; FOLIC ACID BLOOD LEVEL; GENETIC VARIABILITY; GENOTYPE; HUMAN; HYPERTENSION; INCIDENCE; ISCHEMIC HEART DISEASE; LEISURE; MAJOR CLINICAL STUDY; MALE; MORTALITY; NUTRITIONAL PARAMETERS; OBSERVATIONAL STUDY; PHYSICAL ACTIVITY; POPULATION; SYSTOLIC BLOOD PRESSURE; VITAMIN BLOOD LEVEL; BLOOD; COHORT ANALYSIS; FOLLOW UP; GENETIC POLYMORPHISM; GENETICS; GENOTYPING TECHNIQUE; METABOLISM; MIDDLE AGED; RISK FACTOR; YOUNG ADULT;

ADOLESCENT; ADULT; AGED; CARDIOVASCULAR DISEASES; CHOLESTEROL, HDL; CHOLESTEROL, LDL; COHORT STUDIES; DENMARK; DYSLIPIDEMIAS; FEMALE; FOLIC ACID; FOLLOW-UP STUDIES; GENOTYPE; GENOTYPING TECHNIQUES; HOMOCYSTEINE; HUMANS; HYPERTENSION; MALE; METHYLENETETRAHYDROFOLATE REDUCTASE (NADPH2); MIDDLE AGED; POLYMORPHISM, GENETIC; RISK FACTORS; STROKE; TRIGLYCERIDES; VITAMIN B 12; YOUNG ADULT;

EID: 84918792776     PISSN: 14366207     EISSN: 14366215     Source Type: Journal    
DOI: 10.1007/s00394-014-0659-2     Document Type: Article

References (41)

1. Homocysteine studies collaboration (2002) Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. JAMA 288:2015–2022
2. Wald DS, Law M, Morris JK (2002) Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. BMJ 325:1202
3. Toole JF, Malinow MR, Chambless LE, Spence JD, Pettigrew LC et al (2004) Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial. JAMA 291:565–575
4. Lonn E, Yusuf S, Arnold MJ, Sheridan P, Pogue J et al (2006) Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med 354:1567–1577
5. Bonaa KH, Njolstad I, Ueland PM, Schirmer H, Tverdal A et al (2006) Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med 354:1578–1588
6. Ebbing M, Bleie O, Ueland PM, Nordrehaug JE, Nilsen DW et al (2008) Mortality and cardiovascular events in patients treated with homocysteine-lowering B vitamins after coronary angiography: a randomized controlled trial. JAMA 300:795–804
7. Albert CM, Cook NR, Gaziano JM, Zaharris E, MacFadyen J et al (2008) Effect of folic acid and B vitamins on risk of cardiovascular events and total mortality among women at high risk for cardiovascular disease: a randomized trial. JAMA 299:2027–2036
8. Armitage JM, Bowman L, Clarke RJ, Wallendszus K, Bulbulia R et al (2010) Effects of homocysteine-lowering with folic acid plus vitamin B12 vs placebo on mortality and major morbidity in myocardial infarction survivors: a randomized trial. JAMA 303:2486–2494
9. VITATOPS trial study group (2010) B vitamins in patients with recent transient ischaemic attack or stroke in the VITAmins TO Prevent Stroke (VITATOPS) trial: a randomised, double-blind, parallel, placebo-controlled trial. Lancet Neurol 9:855–865
10. Homocysteine Lowering Trialists’ Collaboration (1998) Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials. Homocysteine Lowering Trialists’ Collaboration. BMJ 316:894–898
11. Holmes MV, Newcombe P, Hubacek JA, Sofat R, Ricketts SL et al (2011) Effect modification by population dietary folate on the association between MTHFR genotype, homocysteine, and stroke risk: a meta-analysis of genetic studies and randomised trials. Lancet 378:584–594
12. Huo Y, Qin X, Wang J, Sun N, Zeng Q et al (2012) Efficacy of folic acid supplementation in stroke prevention: new insight from a meta-analysis. Int J Clin Pract 66:544–551
13. Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA et al (1995) A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 10:111–113
14. Husemoen LL, Thomsen TF, Fenger M, Jorgensen HL, Jorgensen T (2003) Contribution of thermolabile methylenetetrahydrofolate reductase variant to total plasma homocysteine levels in healthy men and women. Inter99 (2). Genet Epidemiol 24:322–330
15. Casas JP, Bautista LE, Smeeth L, Sharma P, Hingorani AD (2005) Homocysteine and stroke: evidence on a causal link from mendelian randomisation. Lancet 365:224–232
16. Klerk M, Verhoef P, Clarke R, Blom HJ, Kok FJ et al (2002) MTHFR 677C– > T polymorphism and risk of coronary heart disease: a meta-analysis. JAMA 288:2023–2031
17. Lewis SJ, Ebrahim S, Davey SG (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 331:1053
18. Chiuve SE, Giovannucci EL, Hankinson SE, Hunter DJ, Stampfer MJ et al (2005) Alcohol intake and methylenetetrahydrofolate reductase polymorphism modify the relation of folate intake to plasma homocysteine. Am J Clin Nutr 82:155–162
19. de Bree A, Verschuren WM, Bjorke-Monsen AL, van der Put NM, Heil SG et al (2003) Effect of the methylenetetrahydrofolate reductase 677C– > T mutation on the relations among folate intake and plasma folate and homocysteine concentrations in a general population sample. Am J Clin Nutr 77:687–693
20. Hustad S, Midttun O, Schneede J, Vollset SE, Grotmol T et al (2007) The methylenetetrahydrofolate reductase 677C– > T polymorphism as a modulator of a B vitamin network with major effects on homocysteine metabolism. Am J Hum Genet 80:846–855
21. Davey-Smith G (2010) Mendelian andomization for strengthening causal inference in observational studies: application to gene × environment interactions. Perspectives on Psychological Science 5:527–545
22. Thuesen BH, Husemoen LL, Ovesen L, Jorgensen T, Fenger M et al (2010) Lifestyle and genetic determinants of folate and vitamin B12 levels in a general adult population. Br J Nutr 103:1195–1204
23. Hersoug LG, Husemoen LL, Thomsen SF, Sigsgaard T, Thuesen BH et al (2010) Association of indoor air pollution with rhinitis symptoms, atopy and nitric oxide levels in exhaled air. Int Arch Allergy Immunol 153:403–412
24. Jorgensen T, Borch-Johnsen K, Thomsen TF, Ibsen H, Glumer C et al (2003) A randomized non-pharmacological intervention study for prevention of ischaemic heart disease: baseline results Inter99. Eur J Cardiovasc Prev Rehabil 10:377–386
25. Husemoen LL, Fenger M, Friedrich N, Tolstrup JS, Beenfeldt FS et al (2008) The association of ADH and ALDH gene variants with alcohol drinking habits and cardiovascular disease risk factors. Alcohol Clin Exp Res 32:1984–1991
26. Husemoen LL, Skaaby T, Thuesen BH, Jorgensen T, Fenger RV et al (2012) Serum 25(OH)D and incident type 2 diabetes: a cohort study. Eur J Clin Nutr
27. Husemoen LL, Jorgensen T, Borch-Johnsen K, Hansen T, Pedersen O et al (2010) The association of alcohol and alcohol metabolizing gene variants with diabetes and coronary heart disease risk factors in a white population. PLoS ONE 5:e11735
28. Albrechtsen A, Grarup N, Li Y, Sparso T, Tian G et al (2012) Exome sequencing-driven discovery of coding polymorphisms associated with common metabolic phenotypes. Diabetologia
29. Thuesen BH, Husemoen LL, Fenger M, Linneberg A (2009) Lack of association between the MTHFR (C677T) polymorphism and atopic disease. Clin Respir J 3:102–108
30. Pfeiffer CM, Caudill SP, Gunter EW, Osterloh J, Sampson EJ (2005) Biochemical indicators of B vitamin status in the US population after folic acid fortification: results from the National Health and Nutrition Examination Survey 1999–2000. Am J Clin Nutr 82:442–450
31. Andersen TF, Madsen M, Jorgensen J, Mellemkjoer L, Olsen JH (1999) The Danish national hospital register. A valuable source of data for modern health sciences. Dan Med Bull 46:263–268
32. Juel K, Helweg-Larsen K (1999) The Danish registers of causes of death. Dan Med Bull 46:354–357
33. Brattstrom L, Wilcken DE, Ohrvik J, Brudin L (1998) Common methylenetetrahydrofolate reductase gene mutation leads to hyperhomocysteinemia but not to vascular disease: the result of a meta-analysis. Circulation 98:2520–2526
34. Nygard O, Vollset SE, Refsum H, Stensvold I, Tverdal A et al (1995) Total plasma homocysteine and cardiovascular risk profile. The Hordaland Homocysteine Study. JAMA 274:1526–1533
35. Husemoen LL, Linneberg A, Fenger M, Thuesen BH, Jorgensen T (2009) Changes in lifestyle, biological risk factors and total homocysteine in relation to MTHFR C677T genotype: a 5-year follow-up study. Eur J Clin Nutr 63:1233–1240
36. Husemoen LL, Thomsen TF, Fenger M, Jorgensen T (2006) Changes in lifestyle and total homocysteine in relation to MTHFR(C677T) genotype: the Inter99 study. Eur J Clin Nutr 60:614–622
37. de Bree A, Verschuren WM, Blom HJ (2001) Biological cardiovascular risk factors and plasma homocysteine levels in the general Dutch population. Atherosclerosis 154:513–514
38. Yang Q, Bailey L, Clarke R, Flanders WD, Liu T et al (2012) Prospective study of methylenetetrahydrofolate reductase (MTHFR) variant C677T and risk of all-cause and cardiovascular disease mortality among 6000 US adults. Am J Clin Nutr 95:1245–1253
39. Zee RY, Mora S, Cheng S, Erlich HA, Lindpaintner K et al (2007) Homocysteine, 5,10-methylenetetrahydrofolate reductase 677C > T polymorphism, nutrient intake, and incident cardiovascular disease in 24,968 initially healthy women. Clin Chem 53:845–851
40. Williams C, Kingwell BA, Burke K, McPherson J, Dart AM (2005) Folic acid supplementation for 3 wk reduces pulse pressure and large artery stiffness independent of MTHFR genotype. Am J Clin Nutr 82:26–31
41. Markan S, Sachdeva M, Sehrawat BS, Kumari S, Jain S et al (2007) MTHFR 677 CT/MTHFR 1298 CC genotypes are associated with increased risk of hypertension in Indians. Mol Cell Biochem 302:125–131