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Original Articles

HFE C282Y Homozygosity Is Associated With Lower Total and Low-Density Lipoprotein Cholesterol

The Hemochromatosis and Iron Overload Screening Study

Paul C. Adams, MD; James S. Pankow, PhD, MPH; James C. Barton, MD; Ron T. Acton, PhD; Cathie Leiendecker-Foster, MS; Gordon D. McLaren, MD; Mark Speechley, PhD and John H. Eckfeldt, MD, PhD

From the Department of Medicine (P.C.A.), University Hospital, London, Ontario, Canada; Division of Epidemiology and Community Health (J.S.P.), University of Minnesota, Minneapolis, Minn; Southern Iron Disorders Center (J.C.B.); Division of Microbiology (R.T.A.), University of Alabama, Birmingham, Ala; Veterans Affairs Long Beach Healthcare System (G.D.M.), Long Beach, Calif; Division of Hematology/Oncology (G.D.M.), University of California, Irvine, Calif; Division of Epidemiology and Biostatistics (M.S.), University of Western Ontario, London, Ontario, Canada; and Department of Laboratory Medicine and Pathology (C.L.-F., J.H.E.), University of Minnesota, Minneapolis, Minn.

Correspondence to Paul C. Adams, MD, Department of Medicine, University Hospital, 339 Windermere Rd, London, Ontario, Canada N6A 5A5. E-mail padams{at}uwo.ca

Received August 6, 2008; accepted November 30, 2008.

Background— Previous studies have suggested a positive association of coronary heart disease risk and both serum ferritin concentrations and C282Y heterozygosity. Relationships between serum lipids, C282Y homozygosity, and serum ferritin have not been well established.

Methods and Results— The Hemochromatosis and Iron Overload Screening study screened 101 168 participants in primary care from 5 field centers in the United States and Canada with serum ferritin, transferrin saturation, and HFE genotyping for C282Y and H63D mutations. Serum lipids were measured in a subset of 176 C282Y homozygotes (63 male, 113 female whites) without a prior diagnosis of, family history, or treatment for hemochromatosis and a matched sample of participants with normal transferrin saturation and serum ferritin without C282Y or H63D mutations (wild-type, 123 male, 189 female whites). The proportion of subjects who reported using prescription cholesterol-lowering medications was 3 times higher in HFE wild-type subjects than C282Y homozygotes among men (22% versus 7%; P=0.02) and, in women, 2 times higher (16% versus 8%; P=0.07). After excluding subjects taking cholesterol medications, C282Y homozygotes had significantly lower mean total and low-density lipoprotein cholesterol concentrations than wild-type subjects, with larger genotypic differences for low-density lipoprotein in men (–0.62 mmol/L; 95% CI, –0.93 to –0.33) than in women (–0.28 mmol/L; 95%, CI –0.52 to –0.08).

Conclusions— Total mean serum cholesterol and low-density lipoprotein levels were lower in C282Y homozygotes than in HFE wild-type participants. Further studies are required to determine whether this is related to iron overload, HFE alleles, or other factors on C282Y-positive chromosome 6p haplotypes.

Key Words: hemochromatosis • iron overload • iron

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HFE C282Y Homozygosity Is Associated With Lower Total and Low-Density Lipoprotein Cholesterol: The Hemochromatosis and Iron Overload Screening Study

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