Genetic screening for HFE hemochromatosis in 6,020 Danish men: Penetrance of C282Y, H63D, and S65C variants

Annals of Hematology

Volumn 88, Issue 8, 2009, Pages 775-784

  Pedersen, Palle ^a   Milman, Nils ^a,b  

^a NAESTVED HOSPITAL   (Denmark)

^b Lindevangen 87B   (Denmark)

Author keywords

Genotypes; Hemochromatosis; Mutations; Penetrance; Prevalence; Scandinavia

Indexed keywords

FERRITIN; HFE PROTEIN; IRON; TRANSFERRIN;

ADULT; ARTICLE; BLOOD SAMPLING; CONTROLLED STUDY; DENMARK; FERRITIN BLOOD LEVEL; GENE FREQUENCY; GENE MUTATION; GENETIC SCREENING; GENETIC VARIABILITY; GENOTYPE; HEMOCHROMATOSIS; HETEROZYGOSITY; HOMOZYGOSITY; HUMAN; IRON BLOOD LEVEL; MAJOR CLINICAL STUDY; MALE; PENETRANCE; PHENOTYPE; PHLEBOTOMY; PRIORITY JOURNAL; RESTRICTION FRAGMENT LENGTH POLYMORPHISM; SALIVA ANALYSIS; TRANSFERRIN BLOOD LEVEL;

ADULT; DENMARK; FERRITINS; GENETIC SCREENING; GENOTYPE; HEMOCHROMATOSIS; HUMANS; MALE; MIDDLE AGED; MUTATION, MISSENSE; PENETRANCE; POLYMORPHISM, RESTRICTION FRAGMENT LENGTH; POLYMORPHISM, SINGLE NUCLEOTIDE; TRANSFERRIN;

EID: 67649388066     PISSN: 09395555     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00277-008-0679-1     Document Type: Article

References (33)

1. Milman N, Pedersen P, Steig T, Byg K-E, Graudal N, Fenger K (2001) Clinically overt hereditary hemochromatosis in Denmark 1948-1985: epidemiology, factors of significance for long-term survival, and causes of death in 179 patients. Ann Hematol 80:737-744 doi: 10.1007/ s002770100371
2. Milman N, Pedersen P (2003) Evidence that the Cys282Tyr mutation of the HFE gene originated from a population in Southern Scandinavia and spread with the Vikings. Clin Genet 64:36-47 doi: 10.1034/ j.1399-0004.2003.00083.x
3. Milman N (2000) Inheritance of hemochromatosis: Family studies. In: Barton JC, Edwards CQ (eds) Hemochromatosis. Genetics, pathophysiology, diagnosis and treatment. Cambrigde University Press, Cambrigde, pp 15-41 ISBN 0 521 593808
4. Burt MJ, George PM, Upton JD, Collett JA, Frampton CM, Chapman TM, Walmsley TA, Chapman BA (1998) The significance of haemochromatosis gene mutations in the general population: Implications for screening. Gut 43:830-836
5. Olynyk JK, Cullen DJ, Aquilia S, Rossi E, Summerville L, Powell LW (1999) A population-based study of the clinical expression of the hemochromatosis gene. N Engl J Med 341:718-724 doi: 10.1056/ NEJM199909023411002
6. McDonnell SM, Hover A, Gloe D, Ou CY, Cogswell ME, Grummer-Strawn L (1999) Population-based screening for hemochromatosis using phenotypic and DNA testing among employees of health maintenance organizations in Springfield, Missouri. Am J Med 107:30-37 doi: 10.1016/ S0002-9343(99)00163-1
7. McLaren GD, McLaren CE, Adams PC, Barton JC, Reboussin DM, Gordeuk VR, Acton RT, Harris EL, Speechley MR, Sholinsky P, Dawkins FW, Snively BM, Vogt TM, Eckfeldt JH, Hemochromatosis and Iron Overload Screen (HEIRS) Study Research Investigators (2008) Clinical manifestations of hemochromatosis in HFE C282Y Homozygotes identified by screening. Can J Gastroenterol 22:923-930
8. Phatak PD, Ryan DH, Cappuccio J, Oakes D, Braggins C, Provenzano K, Eberly S, Sham RL (2002) Prevalence and penetrance of HFE mutations in 4865 unselected primary care patients. Blood Cells Mol Dis 29:41-47 doi: 10.1006/bcmd.2002.0536
9. 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 114:474-484 doi: 10.1046/ j.1365-2141.2001.02949.x
10. Beutler E, Felitti VJ, Koziol JA, Ho NJ, Gelbart T (2002) Penetrance of 845G→A (C282Y) HFE hereditary haemochromatosis mutation in the USA. Lancet 359:211-218 doi: 10.1016/S0140-6736(02)07447-0
11. Andersen RV, Tybjærg-Hansen A, Appleyard M, Birgens H, Nordestgaard BG (2004) Hemochromatosis mutations in the general population: Iron overload progression rate. Blood 103:2914-2919 doi: 10.1182/blood-2003-10-3564
12. Allen KJ, Gurrin LC, Osborne NJ, Delatycki MB, Nicoll AJ, McLaren CE, Bahlo M, Nisselle AE, Vulpe CD, Anderson GJ, Southey MC, Giles GG, English DR, Hopper JL, Olynyk JK, Powell LW, Gertig DM (2008) Iron overload related disease in HFE hereditary hemochromatosis. N Engl J Med 358:221-230 doi: 10.1056/NEJMoa073286
13. Elsass P, Pedersen P, Husum K, Milman N (2008) Assessment of the psychological effects of genetic screening of hereditary hemochromatosis. Ann Hematol 87:397-404 doi: 10.1007/s00277-007-0415-2
14. Pedersen P, Melsen GV, Milman N (2008) Frequencies of the haemochromatosis (HFE) gene variants C828Y, H63D and S65C in 6,020 ethnic Danish men. Ann Hematol 87:735-740 doi: 10.1007/s00277-008-0506-8
15. Rudbeck L, Dissing J (1998) Rapid, simple alkaline extraction of human genomic DNA from whole blood, buccal epithelial cells, semen and forensic stains for PCR. Biotechniques 25:588-592
16. Thorstensen K, Asberg A, Kvitland M, Svaasand E, Hveem K, Bjerve KS (2000) Detection of an unusual combination of mutations in the HFE gene for hemochromatosis. Genet Test 4:371-376 doi: 10.1089/109065700750065117
17. Best LG, Harris PE, Spriggs EL (2001) Hemochromatosis mutations C282Y and H63D in "cis" phase. Clin Genet 60:68-72 doi: 10.1034/ j.1399-0004.2001.600111.x
18. Lucotte G, Champenois T, Semonin O (2001) A rare case of a patient heterozygous for the hemochromatosis mutation C282Y and homozygous for H63D. Blood Cells Mol Dis 27:892-893 doi: 10.1006/bcmd.2001.0451
19. Milman N (1991) Iron status markers in hereditary haemochromatosis: distinction between individuals being homozygous and heterozygous for the haemochromatosis allele. Eur J Haematol 47:292-298
20. Hamwi A, Endler G, Rubi K, Wagner O, Endler AT (2002) Reference values for a heterogeneous ferritin assay and traceability to the 3rd International Recombinant Standard for Ferritin (NIBSC code 94/572). Clin Chem Lab Med 40:365-370 doi: 10.1515/CCLM.2002.059
21. Milman N (1996) Serum ferritin in Danes: Studies of iron status from infancy to old age, during blood donation and pregnancy. Int J Hematol 63:103-135 doi: 10.1016/0925-5710(95)00426-2
22. Milman N, Clausen J, Byg K-E (1998) Iron status in 268 Danish women aged 18-30 years: Influence of menstruation, contraceptive method, and iron supplementation. Ann Hematol 77:13-19 doi: 10.1007/s002770050405
23. Milman N, Ovesen L, Byg K-E, Graudal N (1999) Iron status in Danes updated 1994. I: Prevalence of iron deficiency and iron overload in 1332 men aged 40-70 years. Influence of blood donation, alcohol intake, and iron supplementation. Ann Hematol 78:393-400 doi: 10.1007/s002770050537
24. Milman N, Byg K-E, Ovesen L, Kirchhoff M, Jürgensen KS (2002) Iron status in Danish men 1984-94: A cohort comparison of changes in iron stores and the prevalence of iron deficiency and iron overload. Eur J Haematol 68:332-340 doi: 10.1034/j.1600-0609.2002.01668.x
25. Wallace DF, Walker AP, Pietrangelo A, Clare M, Bomford AB, Dixon JL, Powell LW, Subramaniam VN, Dooley JS (2002) Frequency of the S65C mutation of HFE and iron overload in 309 subjects heterozygous for C282Y. J Hepatol 36:474-479 doi: 10.1016/S0168-8278(01)00304-X
26. Asberg A, Thorstensen K, Hveem K, Bjerve KS (2002) Hereditary hemochromatosis: The clinical significance of the S65C mutation. Genet Test 6:59-62 doi: 10.1089/109065702760093933
27. Milman N, Pedersen P, Steig T, Melsen GV (2003) Frequencies of the hereditary hemochromatosis allele in different populations. Comparison of previous phenotypic methods and novel genotypic methods. Int J Hematol 7:48-54 doi: 10.1007/BF02982602
28. Edwards CQ, Kushner JP (1993) Screening for hemochromatosis. N Engl J Med 328:1616-1620 doi: 10.1056/NEJM199306033282208
29. George DK, Powell LW (1997) Review article: The screening, diagnosis and optimal management of haemochromatosis. Aliment Pharmacol Ther 11:631-639 doi: 10.1046/j.1365-2036.1997.00197.x
30. Adams P, Brissot P, Powell LW (2000) EASL International Consensus Conference on Haemochromatosis. J Hepatol 33:485-504 doi: 10.1016/ S0168-8278(01)80874-6
31. Edwards CQ, Griffen LM, Kaplan J, Kushner JP (1989) Twenty-four hour variation of transferrin saturation in treated and untreated haemochromatosis homozygotes. J Intern Med 226:373-379
32. Munro HN, Linder MC (1978) Ferritin: Structure, biosynthesis, and role in iron metabolism. Physiol Rev 58:317-396
33. Allen KJ (2008) Population genetic screening for hereditary haemochromatosis: Are we a step closer? Med J Aust 189:300-301