Adams Paul C, Pankow James S, Barton James C, Acton Ron T, Leiendecker-Foster Cathie, McLaren Gordon D, Speechley Mark, Eckfeldt John H
Department of Medicine, University Hospital, London, Ontario, Canada.
Circ Cardiovasc Genet. 2009 Feb;2(1):34-7. doi: 10.1161/CIRCGENETICS.108.813089. Epub 2009 Jan 23.
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.
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).
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.
既往研究提示冠心病风险与血清铁蛋白浓度及C282Y杂合性均呈正相关。血清脂质、C282Y纯合性与血清铁蛋白之间的关系尚未完全明确。
血色素沉着症和铁过载筛查研究对来自美国和加拿大5个现场中心的101168名初级保健参与者进行了血清铁蛋白、转铁蛋白饱和度检测，并对C282Y和H63D突变进行HFE基因分型。在176名C282Y纯合子（63名男性，113名女性白人）亚组中测量血清脂质，这些参与者既往未被诊断为血色素沉着症，无家族史，也未接受过血色素沉着症治疗，同时选取了转铁蛋白饱和度和血清铁蛋白正常且无C282Y或H63D突变的匹配参与者样本（野生型，123名男性，189名女性白人）。在男性中，报告使用处方降胆固醇药物的受试者比例在HFE野生型受试者中比C282Y纯合子高约3倍（22%对7%；P = 0.02），在女性中高2倍（16%对8%；P = 0.07）。排除服用胆固醇药物的受试者后，C282Y纯合子的平均总胆固醇和低密度脂蛋白胆固醇浓度显著低于野生型受试者，男性低密度脂蛋白的基因型差异（-0.62 mmol/L；95%CI，-0.93至-0.33）大于女性（-0.28 mmol/L；95%CI，-0.52至-0.08）。
C282Y纯合子的平均总血清胆固醇和低密度脂蛋白水平低于HFE野生型参与者。需要进一步研究以确定这是否与铁过载、HFE等位基因或6号染色体p臂C282Y阳性单倍型上的其他因素有关。
