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B-vitamins, homocysteine and gene polymorphism in adults with fasting or post-methionine loading hyperhomocysteinemia

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Abstract

Background

Although fasting and post-methionine loading (PML) homocysteine concentrations are not necessarily related, a high percentage of hyperhomocysteinemia cases would be missed if methionine loading was not performed.

Aim of the study

The influences of B-vitamins and genetic polymorphism (methylenetetrahydrofolate reductase 677C → T, MTHFR 677C → T) on fasting and PML homocysteine concentrations and the relationship between fasting and PML homocysteine were studied.

Methods

This study was a cross-sectional study. Healthy subjects were divided into either fasting hyper-homocysteinemia (≥12.2 µmol/l) (fasting hyper-hcy, n = 51), PML hyper-homocysteinemia (fasting homocysteine <12.2 µmol/l but PML homocysteine ≥25.6 µmol/l) (PML hyper-hcy, n = 29), or normo-homocysteinemia (fasting homocysteine <12.2 µmol/l and PML homocysteine <25.6 µmol/l) (normo-hcy, n = 118) group based on elevated fasting and PML homocysteine levels of the 75th percentile of the population. The concentrations of plasma fasting and PML homocysteine, serum folate, vitamin B-12, plasma pyridoxal 5′- phosphate (PLP) were measured. The genetic polymorphisms were determined.

Results

Fasting homocysteine, but not PML homocysteine and MTHFR 677C → T genotype, was significantly and inversely affected by serum folate concentration after adjusting for potential confounders (β = −0.062, P < 0.01). Fasting and PML homocysteine were highly associated in the fasting hyper-hcy and pooled groups (P < 0.01) but not in the PML hyper-hcy and normo-hcy groups. PML homocysteine did not interact with either serum folate (P = 0.302), vitamin B-12 (P = 0.465), plasma PLP (P = 0.996) or MTHFR 677C → T genotype (P = 0.136) to affect fasting homocysteine concentration.

Conclusions

Approximately one-third (36.3%) of hyperhomocysteinemia cases would be missed if methionine loading were not performed. Even though subjects may have a normal fasting homocysteine concentration, they need further screening for their PML homocysteine.

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References

  1. Araki A, Sako Y (1987) Determination of free and total homocysteine in human plasma by high-performance liquid chromatography with fluorescence detection. J Chromatogr 422: 43–52

    Article  CAS  Google Scholar 

  2. Bates CJ, Pentieva KD, Matthews N, Macdonald A (1999) A simple, sensitive and reproducible assay for pyridoxal 5′-phosphate and 4-pyridoxic acid in human plasma. Chin Chim Acta 280:101–111

    Article  CAS  Google Scholar 

  3. Bostom AG, Jacques PF, Nadeau MR, Williams RR, Ellison RC, Selhub J (1995) Post-methionine load hyperhomocysteinemia in persons with normal fasting total plasma homocysteine: initial results from the NHLBI Family Heart Study. Atherosclerosis 116:147–51

    Article  CAS  Google Scholar 

  4. Boushey CJ, Beresford SA, Omenn GS, Motulsky AG (1995) A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intake. JAMA 274:1049–1057

    Article  CAS  Google Scholar 

  5. Brattström L, Israelsson B, Norrving B, Bergqvist D, Thorne J, Hultberg B, Hamfelt A (1990) Impaired homocysteine metabolism in early-onset cerebral and peripheral occlusive arterial disease. Effects of pyridoxine and folic acid treatment. Atherosclerosis 81:51–60

    Article  Google Scholar 

  6. Clarke R, Armitage J (2000) Vitamin supplements and cardiovascular risk: review of the randomized trials of homocysteine-lowering vitamin supplements. Semin Thromb Hemost 26:341–348

    Article  CAS  Google Scholar 

  7. Clarke R, Daly L, Robinson K, Naughten E, Cahalane S, Fowler B, Graham I (1991) Hyperhomocysteinemia: an independent risk factor for vascular disease. N Engl J Med 324:1149–1155

    CAS  Google Scholar 

  8. Dudman NP, Wilcken DE, Wang J, Lynch JF, Macey D, Lundberg P (1993) Disordered methionine/homocysteine metabolism in premature vascular disease. Its occurrence, cofactor therapy, and enzymology. Arterioscler Thromb 13:1253–1260

    CAS  Google Scholar 

  9. Dunkelgrun M, Hoeks SE, Schouten O, Feringa HHH, Welten GMJM, Vidakovic R, van Gestel YRBM, van Domburg RT, Goei D, de Jonge R, Lindemans J, Poldermans D (2008) Methionine loading does not enhance the predictive value of homocysteine serum testing for all-cause mortality or major adverse cardiac events. Intern Med J (in press)

  10. Durand P, Prost M, Loreau N, Lussier-Cacan S, Blache D (2001) Impaired homocysteine metabolism and atherothrombotic disease. Lab Invest 81:645–672

    Article  CAS  Google Scholar 

  11. Girelli D, Martinelli N, Olivieri O, Pizzolo F, Friso S, Faccini G, Bozzini C, Tenuti I, LottoV Villa G, Guarini P, Trabetti E, Pignatti PF, Mazzucco A, Corrocher R (2006) Hyperhomocysteinemia and mortality after coronary artery bypass grafting. Plos One 1:e83

    Article  CAS  Google Scholar 

  12. Giusti B, Camacho-Vanegas O, Attanosio M, Comeglio P, Gori AM, Brunelli T, Prisco D, Gensini GF, Abbate R, Pepe G (1999) Microheterogeneity in the distribution of the 844ins68 in the cystathionine β-synthase gene in Italy. Thromb Res 94:249–254

    Article  CAS  Google Scholar 

  13. Graham IM, Daly LE, Refsum HM, Robinson K, Brattstrom LE, Ueland PM, Palma-Reis RJ, Boers GH, Sheahan RG, Israelsson B, Uiterwaal CS, Meleady R, McMaster D, Verhoef P, Witteman J, Rubba P, Bellet H, Wautrecht JC, de Valk HW, Sales Luis AC, Parrot-Rouland FM, Tan KS, Higgins I, Garcon D, Andria G (1997) Plasma homocysteine as a risk factor for vascular disease. The European Concerted Action Project. JAMA 277:1775–1781

    Article  CAS  Google Scholar 

  14. Hart SR, Mangoni AA, Swift CG, Jackson SH (2006) Effect of methionine loading on pulse wave analysis in elderly volunteers. Postgrad Med J 82:524–527

    Article  CAS  Google Scholar 

  15. Hart SR, Mangoni AA, Swift CG, Jackson SHD (2006) Lack of significant effects of methionine loading on endothelial function in elderly volunteers. Heat Lung Circ 15:358–361

    Article  CAS  Google Scholar 

  16. Lee BJ, Lin PT, Liaw YP, Chang SJ, Cheng CH, Huang YC (2003) Homocysteine and risk of coronary artery disease: folate is the important determinant of plasma homocysteine concentration. Nutrition 19:577–583

    Article  CAS  Google Scholar 

  17. Lee BJ, Huang MC, Chung LJ, Cheng CH, Lin KL, Su KH, Huang YC (2004) Folic acid and vitamin B-12 are more effective than vitamin B-6 in lowering fasting plasma homocysteine concentration in patients with coronary artery disease. Eur J Clin Nutr 58:481–487

    Article  CAS  Google Scholar 

  18. Ma J, Stampfer MJ, Hennekens CH, Frosst P, Selhub J, Horsford J, Malinow MR, Willett WC, Rozen R (1996) Methylenetetrahydrofolate reductase polymorphism, plasma folate, homocysteine, and risk of myocardial infarction in US physicians. Circulation 94:2410–2416

    CAS  Google Scholar 

  19. Malinow MR, Bostom AG, Krauss RM (1999) Homocyst(e)ine, diet, and cardiovascular diseases: a statement for healthcare professionals from the Nutrition Committee, American Heart Association. Circulation 99:178–82

    CAS  Google Scholar 

  20. Marcucci R, Giusti B, Betti I, Evangelisti L, Fedi S, Sodi A, Cappelli S, Menchini U, Abbate R, Prisco D (2003) Genetic determinants of fasting and post-methionine hyperhomocysteinemia in patients with retinal vein occlusion. Thromb Res 11:7–12

    Article  CAS  Google Scholar 

  21. Miller JW, Nadeau MR, Smith D, Selhub J (1994) Vitamin B–6 deficiency vs folate deficiency: comparison of responses to methionine loading in rats. Am J Clin Nutr 59:1033–1039

    CAS  Google Scholar 

  22. Qujeq D, Omran TS, Hosini L (2001) Correlation between total homocysteine, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol in the serum of patients with myocardial infarction. Clin Biochem 34:97–101

    Article  CAS  Google Scholar 

  23. Refsum H, Ueland PM (1998) Recent data are not in conflict with homocysteine as a cardiovascular risk factor. Curr Opin Lipidol 9:533–539

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  25. Selhub J, Jacques PF, Wilson PW, Rush D, Rosenberg IH (1993) Vitamin status and intake as primary determinants of homocysteinemia in an elderly population. JAMA 270:2693–2698

    Article  CAS  Google Scholar 

  26. Selhub J, Miller JW (1992) Hypothesis—the pathogenesis of homocysteinemia: interruption of the coordinate regulation by S-adenosylmethionine of the remethylation and transsulfuration of homocysteine. Am J Clin Nutr 55:131–138

    CAS  Google Scholar 

  27. Stampfer MJ, Malinow MR, Willett WC, Newcomer LM, Upson B, Ullmann D, Tishler PV, Hennekens CH (1992) A prospective study of plasma homocyst(e)ine and risk of myocardial infarction in US physicians. JAMA 268:877–881

    Article  CAS  Google Scholar 

  28. Tsai MY, Welge BG, Hanson NQ, Bignell MK, Vessey J, Schwichtenberg K, Yang F, Bullemer FE, Rasmussen R, Graham KJ (1999) Genetic causes of mild hyperhomocysteinemia in patients with premature occlusive coronary artery diseases. Atherosclerosis 143:163–170

    Article  CAS  Google Scholar 

  29. Ubbink JB, van der Merwe A, Delport R, Allen RH, Stabler SP, Riezler R, Vermaak WJ (1996) The effect of a subnormal vitamin B-6 status on homocysteine metabolism. J Clin Invest 98:177–184

    Article  CAS  Google Scholar 

  30. Ubbink JB, Vermaak WJ, van der Merwe A, Becker PJ, Delport R, Potgieter HC (1994) Vitamin requirements for the treatment of hyperhomocysteinemia in humans. J Nutr 124:1927–1933

    CAS  Google Scholar 

  31. van den Berg M, de Jong SC, Devillé W, Rauwerda JA, Jakobs C, Pals G, Boers GH, Stehouwer CD (1999) Variability of fasting and post-methionine plasma homocysteine levels in normo- and hyperhomocysteinemia individuals. Neth J Med 55:29–38

    Article  Google Scholar 

  32. van der Griend R, Haas FJLM, Duran M, Biesma DH, Th Meuwissen OJA, Banga JD (1998) Methionine loading test is necessary for detection of hyperhomocysteinemia. J Lab Clin Med 132:67–72

    Article  Google Scholar 

  33. Ventura P, Panini R, Verlato C, Scarpetta G, Salvioli G (2000) Peroxidation indices and total antioxidant capacity in plasma during hyperhomocysteinemia induced by methionine oral loading. Metab Clin Exp 49:225–228

    CAS  Google Scholar 

  34. Verhoef P, Kok FJ, Kluijtmans LA, Blom HJ, Refsum H, Ueland PM, Kruyssen DA (1997) The 677C → T mutation in the methylenetetrahydrofolate reductase gene: associations with plasma total homocysteine levels and risk of coronary atherosclerotic disease. Atherosclerosis 132:105–113

    Article  CAS  Google Scholar 

  35. Verhoef P, Stampfer MJ, Buring JE, Gaziano JM, Allen RH, Stabler SP, Reynolds RD, Kok FJ, Hennekens CH, Willett WC (1996) Homocysteine metabolism and risk of myocardial infarction: relation with vitamin B6, B12, and folate. Am J Epidemiol 143:845–859

    CAS  Google Scholar 

  36. Zhang G, Dai C (2001) Gene polymorphism of homocysteine metabolism-related enzymes in Chinese patients with occlusive coronary artery or cerebral vascular disease. Thromb Res 104:187–195

    Article  CAS  Google Scholar 

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Acknowledgments

We express our sincere appreciation to the subjects for their participation in this trial. We thank the technician and the nurses in Taichung Veterans General Hospital for providing expert assistance in collecting blood samples. This study was supported by a grant from the Department of Health (DOH 94-TD-F-113-038), Taiwan.

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Authors and Affiliations

  1. Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan

    Chien-Hsiung Cheng, Ming-Chih Chou & Tsung-Po Tsai

  2. Critical Care and Respiratory Therapy, Taichung Veterans General Hospital, Taichung, Taiwan

    Chien-Hsiung Cheng

  3. School of Nutrition and Institute of Nutritional Science, Chung Shan Medical University, Taichung, Taiwan

    Yi-Chia Huang & Feng-Pan Chen

  4. Dept. of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan

    Ming-Chih Chou & Tsung-Po Tsai

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  1. Chien-Hsiung Cheng
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Correspondence to Tsung-Po Tsai.

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Cheng, CH., Huang, YC., Chen, FP. et al. B-vitamins, homocysteine and gene polymorphism in adults with fasting or post-methionine loading hyperhomocysteinemia. Eur J Nutr 47, 491–498 (2008). https://doi.org/10.1007/s00394-008-0752-5

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  • DOI: https://doi.org/10.1007/s00394-008-0752-5

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