HFE C282Y homozygosity is associated with lower total and LDL cholesterol: the Hemochromatosis and Iron Overload Screening (HEIRS) Study

Background: Previous studies have suggested a positive association of coronary heart disease (CHD) 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 HEIRS Study screened 101,168 participants in primary care from 5 field centers in the US and Canada with serum ferritin, transferrin saturation (TS), and HFE genotyping for C282Y and H63D mutations. Serum lipids were measured in a subset of 176 C282Y homozygotes (63 male, 113 female Caucasians) 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 Caucasians). The proportion of subjects who reported using prescription cholesterol-lowering medications was approximately three times higher in HFE wild-type subjects than C282Y homozygotes among men (22% vs. 7%; p=0.003) and, in women, two times higher (16% vs. 8%; p=0.05) . After excluding subjects taking cholesterol medications, C282Y homozygotes had significantly lower mean total and LDL-cholesterol concentrations than wild-type subjects, with larger genotypic differences for LDL 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 LDL levels were lower in C282Y homozygotes than in HFE wild type participants. Further studies are required to by gest on A uust 7, 2017 http://circgs.ahajournals.org/ D ow nladed from