Hostname: page-component-cd9895bd7-lnqnp Total loading time: 0 Render date: 2024-12-24T16:05:05.113Z Has data issue: false hasContentIssue false

Risk of iron overload in carriers of genetic mutations associated with hereditary haemochromatosis: UK Food Standards Agency workshop

Published online by Cambridge University Press:  08 March 2007

Mamta Singh*
Affiliation:
Food Standards Agency, Aviation House, 125 Kingsway, London WC2B 6NH, UK
Margaret Ashwell
Affiliation:
Ashwell Associates, Ashwell Street, Ashwell, Hertfordshire SG7 5PZ, UK
Peter Sanderson
Affiliation:
Food Standards Agency, Aviation House, 125 Kingsway, London WC2B 6NH, UK
Janet Cade
Affiliation:
Leeds University, Centre for Epidemiology and Biostatistics, 30–32 Hyde Terrace, Leeds LS2 9JT, UK
Jennifer Moreton
Affiliation:
Leeds University, Centre for Epidemiology and Biostatistics, 30–32 Hyde Terrace, Leeds LS2 9JT, UK
Susan Fairweather-Tait
Affiliation:
Institute of Food Research, Norwich Research Park, Colney, Norwich NR4 7UA, UK
Mark Roe
Affiliation:
Institute of Food Research, Norwich Research Park, Colney, Norwich NR4 7UA, UK
Joannes J. M. Marx
Affiliation:
Eijkman-Winkler Institute for Microbiology, Infections Diseases and Inflammation, University Medical Centre, Utrecht, the Netherlands
Mark Worwood
Affiliation:
University of Wales College of Medicine, Cardiff CF14 4XN, UK
James D. Cook
Affiliation:
University of Kansas Medical Centre, Kansas City, KS 66160, USA
*
*Corresponding author: Ms Mamta Singh, fax +44 20 7276 8906, email [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

The UK Food Standards Agency convened a group of expert scientists to review current research investigating diet and carriers of genetic mutations associated with hereditary haemochromatosis. The workshop concluded that individuals who are heterozygous for the C282Y mutation of the HFE gene do not appear to respond abnormally to dietary Fe and therefore do not need to change their diet to prevent accumulation of body Fe.

Type
Workshop Report
Copyright
Copyright © The Nutrition Society 2006

References

Beutler, E, Felitti, VJ, Koziol, JA, Ho, NJ & Gelbart, T (2002)Penetrance of 845G→A (C282Y) HFE hereditary haemochromatosis mutation in the USA. Lancet 359, 211218.CrossRefGoogle Scholar
Bothwell, TH & MacPhail, AP (1998)Hereditary hemochromatosis: etiologic, pathologic, and clinical aspects. Semin Hematol 35, 5571.Google ScholarPubMed
Cade, JE, Moreton, JA, O'Hara, B, Greenwood, DC, Moor, J, Burley, VJ, Kukalizch, K, Bishop, DT & Worwood, M (2005)Diet and genetic factors associated with iron status in middle-aged women. Am J Clin Nutr 82, 813820.CrossRefGoogle ScholarPubMed
Cook, JD, Flowers, CH & Skikne, BS (2003)The quantitative assessment of body iron. Blood 101, 33593364.CrossRefGoogle ScholarPubMed
Coppin, H, Bensaid, M, Fruchon, S, Borot, N, Blanche, H & Roth, MP (2003)Longevity and carrying the C282Y mutation for haemochromatosis on the HFE gene: case control study of 492 French centenarians. BMJ 327, 132133.CrossRefGoogle ScholarPubMed
Danesh, J & Appleby, P (1999) Coronary heart disease and iron status: meta-analyses of prospective studies. Circulation 99, 852854.CrossRefGoogle ScholarPubMed
Danesh, J, Collins, R, Appleby, P & Peto, R (1998) Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease: meta-analyses of prospective studies. JAMA 279, 14771482.CrossRefGoogle ScholarPubMed
de Valk, B, Addicks, MA, Gosriwatana, I, Lu, S, Hider, RC & Marx, JJ (2000) Non-transferrin-bound iron is present in serum of hereditary haemochromatosis heterozygotes. Eur J Clin Invest 30, 248251.CrossRefGoogle ScholarPubMed
Ellervik, C, Tybjaerg-Hansen, A, Grande, P, Appleyard, M & Nordestgaard, BG (2005) Hereditary hemochromatosis and risk of ischemic heart disease: a prospective study and a case-control study. Circulation 112, 185193.CrossRefGoogle ScholarPubMed
Feder, JN, Gnirke, A & Thomas, W, et al. (1996) A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nat Genet 13, 399408.CrossRefGoogle ScholarPubMed
Greenwood, DC, Cade, JE, Moreton, JA, O'Hara, B, Burley, VJ, Randerson-Moor, JA, Kukalizch, K, Thompson, D, Worwood, M & Bishop, DT (2005) HFE genotype modifies the influence of heme iron intake on iron status. Epidemiology 16, 802805.CrossRefGoogle ScholarPubMed
Grootveld, M, Bell, JD, Halliwell, B, Aruoma, OI, Bomford, A & Sadler, PJ (1989) Non-transferrin-bound iron in plasma or serum from patients with idiopathic hemochromatosis. Characterization by high performance liquid chromatography and nuclear magnetic resonance spectroscopy. J Biol Chem 264, 44174422.CrossRefGoogle ScholarPubMed
Gunn, IR, Maxwell, FK, Gaffney, D, McMahon, AD & Packard, CJ (2004) Haemochromatosis gene mutations and risk of coronary heart disease: a west of Scotland coronary prevention study (WOSCOPS) substudy. Heart 90, 304306.CrossRefGoogle Scholar
Hunt, JR & Zeng, H (2004) Iron absorption by heterozygous carriers of the HFE C282Y mutation associated with hemochromatosis. Am J Clin Nutr 80, 924931.CrossRefGoogle ScholarPubMed
Jackson, HA, Carter, K, Darke, C, Guttridge, MG, Ravine, D, Hutton, RD, Napier, JA & Worwood, M (2001) HFE mutations, iron deficiency and overload in 10, 500 blood donors. Br J Haematol 114, 474484.CrossRefGoogle Scholar
Kartikasari, AE, Georgiou, NA, Visseren, FL, Kats-Renaud, H, van Asbeck, BS & Marx, JJM (2004) Intracellular labile iron modulates adhesion of human monocytes to human endothelial cells. Arterioscler Thromb Vasc Biol 24, 22572262.CrossRefGoogle ScholarPubMed
Kemna, E, Tjalsma, H, Laarakkers, C, Nemeth, E, Willems, H & Swinkels, D (2005) Novel urine hepcidin assay by mass spectrometry. Blood 106, 32683270.CrossRefGoogle ScholarPubMed
Kiechl, S, Willeit, J, Egger, G, Poewe, W & Oberhollenzer, F (1997) Body iron stores and the risk of carotid atherosclerosis: prospective results from the Bruneck Study. Circulation 96, 33003307.CrossRefGoogle ScholarPubMed
Knuiman, MW, Divitini, ML, Olynyk, JK, Cullen, DJ & Bartholomew, HC (2003) Serum ferritin and cardiovascular disease: a 17-year follow-up study in Busselton, Western Australia. Am J Epidemiol 158, 144149.CrossRefGoogle ScholarPubMed
Kooistra, MP, Kersting, S, Gosriwatana, I, Lu, S, Nijhoff-Schutte, J, Hider, RC & Marx, JJ (2002) Nontransferrin-bound iron in the plasma of haemodialysis patients after intravenous iron saccharate infusion. Eur J Clin Invest 32, Suppl. 13641.CrossRefGoogle ScholarPubMed
Lynch, SR, Skikne, BS & Cook, JD (1989) Food iron absorption in idiopathic hemochromatosis. Blood 74, 21872193.CrossRefGoogle ScholarPubMed
McCune, CA, Al Jader, LN, May, A, Hayes, SL, Jackson, HA & Worwood, M (2002) Hereditary haemochromatosis: only 1 % of adult HFE C282Y homozygotes in South Wales have a clinical diagnosis of iron overload. Hum Genet 111, 538543.CrossRefGoogle ScholarPubMed
Merryweather-Clarke, AT, Pointon, JJ, Jouanolle, AM, Rochette, J & Robson, KJ (2000) Geography of HFE C282Y and H63D mutations. Genet Test 4, 183198.CrossRefGoogle ScholarPubMed
Nemeth, E, Tuttle, MS, Powelson, J, Vaughn, MB, Donovan, A, Ward, DM, Ganz, T & Kaplan, J (2004) Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 306, 20902093.CrossRefGoogle ScholarPubMed
Rasmussen, ML, Folsom, AR, Catellier, DJ, Tsai, MY, Garg, U & Eckfeldt, JH (2001) A prospective study of coronary heart disease and the hemochromatosis gene (HFE) C282Y mutation: the Atherosclerosis Risk in Communities (ARIC) study. Atherosclerosis 154, 739746.CrossRefGoogle ScholarPubMed
Reunanen, A, Takkunen, H, Knekt, P, Seppanen, R & Aromaa, A (1995) Body iron stores, dietary iron intake and coronary heart disease mortality. J Intern Med 238, 223230.CrossRefGoogle ScholarPubMed
Roe, MA, Heath, AL, Oyston, SL, Macrow, C, Hoogewerff, JA, Foxall, R, Dainty, JR, Majsak-Newman, G, Willis, G, Fairweather-Tait, SJ (2005) Iron absorption in male C282Y heterozygotes. Am J Clin Nutr 81, 814821.CrossRefGoogle ScholarPubMed
Roest, M, van der, Schouw, YT, de, Valk, B, Marx, JJ, Tempelman, MJ, de Groot, PG, Sixma, JJ & Banga, JD (1999) Heterozygosity for a hereditary hemochromatosis gene is associated with cardiovascular death in women. Circulation 100, 12681273.CrossRefGoogle ScholarPubMed
Roetto, A, Papanikolaou, G, Politou, M, Alberti, F, Girelli, D, Christakis, J, Loukopoulos, D & Camaschella, C (2003) Mutant antimicrobial peptide hepcidin is associated with severe juvenile hemochromatosis. Nat Genet 33, 2122.CrossRefGoogle ScholarPubMed
Salonen, JT, Nyyssonen, K, Korpela, H, Tuomilehto, J, Seppanen, R & Salonen, R (1992) High stored iron levels are associated with excess risk of myocardial infarction in eastern Finnish men. Circulation 86, 803811.CrossRefGoogle ScholarPubMed
Sempos, CT, Looker, AC, Gillum, RF & Makuc, DM (1994) Body iron stores and the risk of coronary heart disease. N Engl J Med 330, 11191124.CrossRefGoogle ScholarPubMed
Sullivan, JL (1981) Iron and the sex difference in heart disease risk. Lancet i, 12931294.CrossRefGoogle Scholar
Swinkels, DW, Janssen, MC, Bergmans, J & Marx, JJM (2006) Hereditary hemochromatosis: genetic complexity and new diagnostic approaches. Clin Chem 52, 950968.CrossRefGoogle ScholarPubMed
The UK Haemochromatosis Consortium (1997) A simple genetic test identifies 90 % of UK patients with haemochromatosis. Gut 41, 841844.CrossRefGoogle Scholar
Tuomainen, TP, Kontula, K, Nyyssonen, K, Lakka, TA, Helio, T & Salonen, JT (1999) Increased risk of acute myocardial infarction in carriers of the hemochromatosis gene Cys282Tyr mutation: a prospective cohort study in men in eastern Finland. Circulation 100, 12741279.CrossRefGoogle ScholarPubMed
Tuomainen, TP, Punnonen, K, Nyyssonen, K & Salonen, JT (1998) Association between body iron stores and the risk of acute myocardial infarction in men. Circulation 97, 14611466.CrossRefGoogle ScholarPubMed
van der A, DL, Grobbee, DE, Roest, M, Marx, JJM, Voorbij, HA & van der Schouw, YT (2005) Serum ferritin is a risk factor for stroke in postmenopausal women. Stroke 36, 16371641.CrossRefGoogle ScholarPubMed
van der A, DL, Marx, JJM, Grobbee, DE, Kamphuis, MH, Georgiou, NA, van kats-Renaud, JH, Breuer, W, Cabantchik, ZI, Roest, M & Voorbij, HA (2006) Non-transferrin-bound iron and risk of coronary heart disease in postmenopausal women. Circulation 113, 19421949.CrossRefGoogle ScholarPubMed
Willis, G, Wimperis, JZ, Smith, KC, Fellows, IW & Jennings, BA (1999) Haemochromatosis gene C282Y homozygotes in an elderly male population. Lancet 354, 221222.CrossRefGoogle Scholar
Wolff, B, Volzke, H, Ludemann, J, Robinson, D, Vogelgesang, D, Staudt, A, Kessler, C, Dahm, JB, John, U & Felix, SB (2004) Association between high serum ferritin levels and carotid atherosclerosis in the Study of Health in Pomerania (SHIP). Stroke 35, 453457.CrossRefGoogle ScholarPubMed