Nassar B A, Zayed E M, Title L M, O'Neill B J, Bata I R, Kirkland S A, Dunn J, Dempsey G I, Tan M H, Johnstone D E
Department of Pathology, Dalhousie University Faculty of Medicine, Halifax, Nova Scotia.
Can J Cardiol. 1998 Feb;14(2):215-20.
To determine the impact of mutations in the HFE gene (human leukocyte antigen H) on predisposition to coronary artery disease (CAD) in patients not diagnosed with hereditary hemochromatosis.
Elevated iron stores can predispose to acute myocardial infarction. Two mutations (C282Y and H63D) in the novel major histocompatibility complex (MHC) class 1 gene HFE were found in most patients with hereditary hemochromatosis causing high iron stores. The effect of these mutations on predisposition to CAD has not been investigated previously.
Three hundred patients with a history of myocardial infarction or angina pectoris and angiographically documented CAD were studied. Patients were divided into two groups: group 1 (150 patients), manifesting early onset CAD and presenting with these findings under age 50 years; and group 2 (150 patients), presenting for the first time over age 65 years. Prevalence of the C282Y and H63D mutations was assessed by molecular analysis, and plasma ferritin was measured immunochemically.
There was no difference in the prevalence of homozygous, heterozygous or compound heterozygous (C282Y/H63D) states between the groups. Males in group 1 had higher plasma ferritin than those in group 2 (234 +/- 174 micrograms/L versus 136 +/- 103 micrograms/L, P < 0.0001), but this was not significantly different in females (75 +/- 54 micrograms/L versus 92 +/- 73 micrograms/L, P = 0.26). Ferritin remained higher in group 1 than in group 2 males after exclusion of mutation carriers (195 +/- 121 micrograms/L versus 109 +/- 76 micrograms/L, respectively, P < 0.0001), but did not change in females.
Higher iron stores were found in males with early onset CAD. This association was not related to the C282Y or H63D mutation in HFE. It is suggested that association of the MHC locus with delayed onset CAD is probably unrelated to HFE in these patients, and that HFE mutations are not a major risk factor in the development of high iron stores in early onset CAD.
确定HFE基因（人类白细胞抗原H）突变对未诊断为遗传性血色素沉着症的患者患冠状动脉疾病（CAD）易感性的影响。
铁储存升高可导致急性心肌梗死。在大多数导致高铁储存的遗传性血色素沉着症患者中发现了新的主要组织相容性复合体（MHC）I类基因HFE中的两种突变（C282Y和H63D）。这些突变对CAD易感性的影响此前尚未得到研究。
对300例有心肌梗死或心绞痛病史且经血管造影证实患有CAD的患者进行研究。患者分为两组：第1组（150例患者），表现为早发性CAD且在50岁以下出现这些症状；第2组（150例患者），首次发病年龄超过65岁。通过分子分析评估C282Y和H63D突变的患病率，并采用免疫化学方法测定血浆铁蛋白。
两组之间纯合子、杂合子或复合杂合子（C282Y/H63D）状态的患病率无差异。第1组男性的血浆铁蛋白高于第2组男性（234±174微克/升对136±103微克/升，P<0.0001），但女性差异无统计学意义（75±54微克/升对92±73微克/升，P = 0.26）。排除突变携带者后，第1组男性的铁蛋白仍高于第2组男性（分别为195±121微克/升对109±76微克/升，P<0.0001），但女性无变化。
早发性CAD男性的铁储存较高。这种关联与HFE基因中的C282Y或H63D突变无关。提示在这些患者中，MHC基因座与迟发性CAD的关联可能与HFE无关，且HFE突变不是早发性CAD中铁储存升高的主要危险因素。
