Barton JC, Barton JC, Adams PC

Language: English
References: 41
Page: 802-811
PDF size: 222.10 Kb.

ABSTRACT

Background. 373 black participants had elevated screening and post-screening serum ferritin (SF) (› 300 µg/L men; › 200 µg/L women). Material and methods. We retrospectively studied SF and post-screening age; sex; body mass index; transferrin saturation (TS); ALT; AST; GGT; elevated C-reactive protein; β-thalassemia; neutrophils; lymphocytes; monocytes; platelets; metacarpophalangeal joint hypertrophy; hepatomegaly; splenomegaly; diabetes; HFE H63D positivity; iron/alcohol intakes; and blood/ erythrocyte transfusion units. Liver disease was defined as elevated ALT or AST. We computed correlations of SF and TS with: age; body mass index; ALT; AST; GGT; C-reactive protein; blood cell counts; and iron/alcohol. We compared participants with SF › 1,000 and ≤ 1,000 µ/L and performed regressions on SF. Results. There were 237 men (63.5%). Mean age was 55 ± 13 (SD) y. 143 participants had liver disease (62 hepatitis B or C). There were significant correlations of SF: TS, ALT, AST, GGT, and monocytes (positive); and SF and TS with platelets (negative). 22 participants with SF › 1,000 µg/L had significantly higher median TS, ALT, and AST, and prevalences of anemia and transfusion › 10 units; and lower median platelets. Regression on SF revealed significant associations: TS; male sex; age; GGT; transfusion units (positive); and splenomegaly (negative) (p ‹ 0.0001, 0.0016, 0.0281, 0.0025, 0.0001, and 0.0096, respectively). Five men with SF › 1,000 µg/L and elevated TS had presumed primary iron overload (hemochromatosis). Four participants had transfusion iron overload. Conclusion. Persistent hyperferritinemia in 373 black adults was associated with male sex, age, TS, GGT, and transfusion. 2.4% had primary iron overload (hemochromatosis) or transfusion iron overload.

REFERENCES

1. Perry GS, Byers T, Yip R, Margen S. Iron nutrition does not account for the hemoglobin differences between blacks and whites. J Nutr 1992; 122: 1417-24.

2. Barton JC, Acton RT, Dawkins FW, Adams PC, Lovato L, Leiendecker-Foster C, McLaren CE, et al. Initial screening transferrin saturation values, serum ferritin concentrations, and HFE genotypes in whites and blacks in the Hemochromatosis and Iron Overload Screening Study. Genet Test 2005; 9: 231-41.

3. Shan Y, Lambrecht RW, Bonkovsky HL. Association of hepatitis C virus infection with serum iron status: analysis of data from the third National Health and Nutrition Examination Survey. Clin Infect Dis 2005; 40: 834-41.

4. Lipschitz DA, Cook JD, Finch CA. A clinical evaluation of serum ferritin as an index of iron stores. N Engl J Med 1974; 290: 1213-16.

5. Nielsen P, Günther U, Dürken M, Fischer R, Dullmann J. Serum ferritin iron in iron overload and liver damage: correlation to body iron stores and diagnostic relevance. J Lab Clin Med 2000; 135: 413-8.

6. Adams PC, Barton JC. A diagnostic approach to hyperferritinemia with a non-elevated transferrin saturation. J Hepatol 2011; 55: 453-8.

7. Moirand R, Lescoat G, Delamaire D, Lauvin L, Campion JP, Deugnier Y, Brissot P. Increase in glycosylated and nonglycosylated serum ferritin in chronic alcoholism and their evolution during alcohol withdrawal. Alcohol Clin Exp Res 1991; 15: 963-9.

8. Kannengiesser C, Jouanolle AM, Hetet G, Mosser A, Muzeau F, Henry D, Bardou-Jacquet E, et al. A new missense mutation in the L ferritin coding sequence associated with elevated levels of glycosylated ferritin in serum and absence of iron overload. Haematologica 2009; 94: 335-9.

9. Adams PC, Reboussin DM, Barton JC, McLaren CE, Eckfeldt JH, McLaren GD, Dawkins FW, et al. Hemochromatosis and iron-overload screening in a racially diverse population. N Engl J Med 2005; 352: 1769-78.

10. McLaren GD, McLaren CE, Adams PC, Barton JC, Reboussin DM, Gordeuk VR, Acton RT, et al. Clinical manifestations of hemochromatosis in HFE C282Y homozygotes identified by screening. Can J Gastroenterol 2008; 22: 923-30.

11. Barton JC, Lafreniere SA, Leiendecker-Foster C, Li H, Acton RT, Press RD, Eckfeldt JH. HFE, SLC40A1, HAMP, HJV, TFR2, and FTL mutations detected by denaturing high-performance liquid chromatography after iron phenotyping and HFE C282Y and H63D genotyping in 785 HEIRS Study participants. Am J Hematol 2009; 84: 710-4.

12. Gordeuk VR, Lovato L, Barton J, Vitolins M, McLaren G, Acton R, McLaren C, et al. Dietary iron intake and serum ferritin concentration in 213 patients homozygous for the HFE C282Y hemochromatosis mutation. Can J Gastroenterol 2012; 26: 345-9.

13. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2013; 36(Suppl. 1): S67- S74.

14. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412-9.

15. Acton RT, Barton JC, Barton JC. Serum ferritin, insulin resistance, and metabolic syndrome: clinical and laboratory associations in 769 non-Hispanic whites without diabetes mellitus in the HEIRS Study. Metab Syndr Relat Disord 2015; 13: 57-63.

16. Borgna-Pignatti C, Galanello R. In: Greer JP, Arber DA, Glader B, List AF, Means RTJr, Paraskevas F, Rodgers GM (Eds.). Wintrobe's Clinical Hematology. 14th ed. Philadelphia. Wolters Kluwer/Lippincott Williams & Wilkins; 2014, pp. 862-913.

17. Vichinsky E. Hemoglobin E syndromes. Hematology: American Society of Hematology Education Program 2007; 2007: 79-83.

18. Gordeuk VR, Reboussin DM, McLaren CE, Barton JC, Acton RT, McLaren GD, Harris EL, et al. Serum ferritin concentrations and body iron stores in a multicenter, multiethnic primary- care population. Am J Hematol 2008; 83: 618-26.

19. Gordeuk VR, Diaz SF, Onojobi GO, Kasvosve I, Debebe Z, Edossa A, Pantin JM, et al. Ferroportin Q248h, dietary iron, and serum ferritin in community African-Americans with low to high alcohol consumption. Alcohol Clin Exp Res 2008; 32: 1947-53.

20. Forde KA, Tanapanpanit O, Reddy KR. Hepatitis B and C in African Americans: current status and continued challenges. Clin Gastroenterol Hepatol 2014; 12: 738-48.

21. Ioannou GN, Dominitz JA, Weiss NS, Heagerty PJ, Kowdley KV. Racial differences in the relationship between hepatitis C infection and iron stores. Hepatology 2003; 37: 795-801.

22. Phillips ML, Boase S, Wahlroos S, Dugar M, Kow L, Stahl J, Slavotinek JP, et al. Associates of change in liver fat content in the morbidly obese after laparoscopic gastric banding surgery. Diabetes Obes Metab 2008; 10: 661-7.

23. Tsimihodimos V, Gazi I, Kalaitzidis R, Elisaf M, Siamopoulos KC. Increased serum ferritin concentrations and liver enzyme activities in patients with metabolic syndrome. Metab Syndr Relat Disord 2006; 4: 196-203.

24. Beaton MD, Chakrabarti S, Adams PC. Inflammation is not the cause of an elevated serum ferritin in non-alcoholic fatty liver disease. Ann Hepatol 2014; 13: 353-6.

25. Angulo P. Nonalcoholic fatty liver disease. N Engl J Med 2002; 346: 1221-31.

26. Ford ES, Cogswell ME. Diabetes and serum ferritin concentration among U.S. adults. Diabetes Care 1999; 22: 1978-83.

27. Yeap BB, Divitini ML, Gunton JE, Olynyk JK, Beilby JP, Mc- Quillan B, Hung J, et al. Higher ferritin levels, but not serum iron or transferrin saturation, are associated with Type 2 diabetes mellitus in adult men and women free of genetic haemochromatosis. Clin Endocrinol (Oxford) 2014

28. Adams PC. Diabetes: Serum ferritin levels and T2DM--are body iron stores elevated? Nat Rev Endocrinol 2012; 8: 573-5.

29. Jehn M, Clark JM, Guallar E. Serum ferritin and risk of the metabolic syndrome in U.S. adults. Diabetes Care 2004; 27: 2422-8.

30. Jones BM, Worwood M, Jacobs A. Isoferritins in normal leucocytes. Br J Haematol 1983; 55: 73-81.

31. Worwood M, Hourahane D, Jones BM. Accumulation and release of isoferritins during incubation in vitro of human peripheral blood mononuclear cells. Br J Haematol 1984; 56: 31-43.

32. Hancox SH, Smith BC. Liver disease as a cause of thrombocytopenia. QJM 2013; 106: 425-31.

33. Bell H, Skinningsrud A, Raknerud N, Try K. Serum ferritin and transferrin saturation in patients with chronic alcoholic and non-alcoholic liver diseases. J Intern Med 1994; 236: 315- 22.

34. Barton JC, Edwards CQ, Bertoli LF, Shroyer TW, Hudson SL. Iron overload in African Americans. Am J Med 1995; 99: 616-23.

35. Wurapa RK, Gordeuk VR, Brittenham GM, Khiyami A, Schechter GP, Edwards CQ. Primary iron overload in African Americans. Am J Med 1996; 101: 9-18.

36. Jones E, Pasricha SR, Allen A, Evans P, Fisher CA, Wray K, Premawardhena A, et al. Hepcidin is suppressed by erythropoiesis in hemoglobin E beta-thalassemia and betathalassemia trait. Blood 2015; 125: 873-80.

37. Lee PL, Reid TJ, III, Bottomley SS, Barton JC. Sideroblastic anemia, iron overload, and ALAS2 R452S in African-American males: phenotype and genotype features of five unrelated patients. Am J Hematol 2011; 86: 787-9.

38. Means RTJr. In: Greer JP, Arber DA, Glader B, List AF, Means RTJr, Paraskevas F, Rodgers GM (Eds.). Wintrobe's Clinical Hematology. 14th ed. Philadelphia. Wolters Kluwer/ Lippincott Williams & Wilkins, 2014, p. 998-1011.

39. Li J, Lange LA, Duan Q, Lu Y, Singleton AB, Zonderman AB, Evans MK, et al. Genome-wide admixture and association study of serum iron, ferritin, transferrin saturation and total iron binding capacity in African Americans. Hum Mol Genet 2015; 24: 572-81.

40. Gichohi-Wainaina WN, Tanaka T, Towers GW, Verhoef H, Veenemans J, Talsma EF, Harryvan J, et al. Associations between common variants in iron-related genes with haematological traits in populations of African ancestry. PLoS One 2016; 11: e0157996.

41. Adams P, Barton JC, McLaren GD, Acton RT, Speechley M, McLaren CE, Reboussin DM, et al. Screening for iron overload: lessons from the Hemochromatosis and Iron Overload Screening (HEIRS) Study. Can J Gastroenterol 2009; 23: 769-72.