title: HFE C282Y homozygotes have reduced low-density lipoprotein cholesterol: the Atherosclerosis Risk in Communities (ARIC) Study.
abstract: Recent studies have raised questions about the long-term health risks for individuals with mutations in the HFE gene, although previous studies may have been plagued by selection bias or lack of population-based comparison groups. We examined cardiovascular disease risk factors and iron and liver biomarkers, as well as morbidity and mortality associated with the C282Y and H63D variants of HFE in the Atherosclerosis Risk in Communities (ARIC) study, which is a population-based cohort of nearly 16,000 U.S. white and black men and women who were 45-64 years old at baseline. Subjects were followed for an average of 15 years for death, incident coronary heart disease, stroke, and heart failure, and an average of 8 years for incident diabetes. The prevalence of C282Y homozygosity was 0.42% (45/10,800) in whites, which is similar to other North American population-based studies. C282Y homozygotes had significantly lower mean low-density lipoprotein (LDL) cholesterol and fibrinogen as well as higher mean levels of iron (ferritin, transferrin saturation) and liver biomarkers (alanine aminotransferase, Hepascore) compared with HFE wild-type subjects. Rates of all-cause mortality, cardiovascular disease, and diabetes were similar across HFE genotypes. These prospective, population-based data indicate higher serum iron indices and possible mild liver dysfunction or disease in some C282Y homozygotes, but they provide little evidence that HFE C282Y or H63D mutations are related to all-cause mortality, cardiovascular disease, or diabetes. Reduced LDL in C282Y homozygotes may be because of effects of excess iron on cholesterol metabolism and lipoprotein formation in the liver.
authors.affiliation: Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, Minn 55454, USA. pankow@umn.edu
authors.forename: James S
authors.initials: JS
authors.lastname: Pankow
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.forename: Paul C
authors.initials: PC
authors.lastname: Adams
authors.forename: Eliseo
authors.initials: E
authors.lastname: Guallar
authors.forename: Catherine
authors.initials: C
authors.lastname: Leiendecker-Foster
authors.forename: Jason
authors.initials: J
authors.lastname: Rogowski
authors.forename: John H
authors.initials: JH
authors.lastname: Eckfeldt
mesh_terms: D001741:Black or African American; D000410:Alanine Transaminase / Q000097:blood; D015415:Biomarkers / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood*; D015331:Cohort Studies; D003327:Coronary Disease / Q000209:etiology; D048909:Diabetes Complications; D005260:Female; D005293:Ferritins / Q000097:blood; D005787:Gene Frequency; D006432:Hemochromatosis / Q000150:complications / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007501:Iron / Q000097:blood; D008107:Liver Diseases / Q000209:etiology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D015995:Prevalence; D011446:Prospective Studies; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D044465:White People
chemical_list: D015415:Biomarkers; D008078:Cholesterol, LDL; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D005293:Ferritins; D007501:Iron; D000410:Alanine Transaminase