title: HFE C282Y homozygosity is associated with lower total and low-density lipoprotein cholesterol: The hemochromatosis and iron overload screening study.
abstract: 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.
  
  
  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 approximately 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.
authors.affiliation: Department of Medicine, University Hospital, London, Ontario, Canada. padams@uwo.ca
authors.forename: Paul C
authors.initials: PC
authors.lastname: Adams
authors.forename: James S
authors.initials: JS
authors.lastname: Pankow
authors.forename: James C
authors.initials: JC
authors.lastname: Barton
authors.forename: Ron T
authors.initials: RT
authors.lastname: Acton
authors.forename: Cathie
authors.initials: C
authors.lastname: Leiendecker-Foster
authors.forename: Gordon D
authors.initials: GD
authors.lastname: McLaren
authors.forename: Mark
authors.initials: M
authors.lastname: Speechley
authors.forename: John H
authors.initials: JH
authors.lastname: Eckfeldt
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D019943:Amino Acid Substitution; D005260:Female; D005293:Ferritins / Q000097:blood; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006432:Hemochromatosis / Q000235:genetics*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D019190:Iron Overload / Q000235:genetics*; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D008403:Mass Screening; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014168:Transferrin / Q000378:metabolism
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D014168:Transferrin; D005293:Ferritins