van der A Daphne L, Rovers Maroeska M, Grobbee Diederick E, Marx Joannes J M, Waalen Jill, Ellervik Christina, Nordestgaard Børge G, Olynyk John K, Mills Peter R, Shepherd James, Grandchamp Bernard, Boer Jolanda M A, Caruso Calogero, Arca Marcello, Meyer Beat J, van der Schouw Yvonne T
Center for Nutrition and Health, Postbak 84, National Institute for Public Health and the Environment, PO Box 1, 3720 BA Bilthoven, The Netherlands.
Circ Cardiovasc Genet. 2008 Oct;1(1):43-50. doi: 10.1161/CIRCGENETICS.108.773176.
Whether mutations in the hemochromatosis (HFE) gene increase cardiovascular disease risk is still undetermined. The main reason is the low frequency of the mutations, in particular of the compound C282Y/H63D genotype. We combined the data of 11 observational studies for an individual patient data meta-analysis.
Individual patient data were obtained from published as well as unpublished studies that had information available on the C282Y mutation as well as the H63D mutation in relation to coronary heart disease risk. Individual records were provided on each of the 53 880 participants in 11 studies. In total, 10 541 patients with coronary events were documented, of whom 5724 had an acute myocardial infarction. The crude and adjusted association between HFE genotypes and coronary events was examined by logistic regression analysis. We explored potential effect modification of the association between traditional cardiovascular risk factors and coronary events by HFE genotypes. After full adjustment, the odds ratio for coronary heart disease was 1.12 (95% CI, 0.92 to 1.37) for subjects with the compound heterozygous (C282Y/H63D) genotype relative to those with the wild-type/wild-type genotype. The odds ratios for C282Y/C282Y, C282Y/wild-type, H63D/H63D, and H63D/wild-type were 0.78 (95% CI, 0.49 to 1.26), 0.98 (95% CI, 0.90 to 1.07), 1.16 (95% CI, 0.97 to 1.38), and 1.07 (95% CI, 1.00 to 1.14), respectively. There was no evidence for effect modification.
The results of this large individual patient data meta-analysis do not support the view that HFE gene mutations are associated with an increased risk of coronary heart disease or acute myocardial infarction.
血色素沉着症（HFE）基因突变是否会增加心血管疾病风险仍未确定。主要原因是这些突变的频率较低，尤其是复合杂合子C282Y/H63D基因型。我们合并了11项观察性研究的数据，进行个体患者数据的荟萃分析。
个体患者数据来自已发表和未发表的研究，这些研究提供了与冠心病风险相关的C282Y突变以及H63D突变的信息。11项研究中的53880名参与者都有各自的记录。总共记录了10541例冠心病事件患者，其中5724例发生急性心肌梗死。通过逻辑回归分析检验HFE基因型与冠心病事件之间的原始关联和校正关联。我们探讨了HFE基因型对传统心血管危险因素与冠心病事件之间关联的潜在效应修正作用。完全校正后，复合杂合子（C282Y/H63D）基因型受试者患冠心病的比值比为1.12（95%CI，0.92至1.37），相对于野生型/野生型基因型受试者。C282Y/C282Y、C282Y/野生型、H63D/H63D和H63D/野生型的比值比分别为0.78（95%CI，0.49至1.26）、0.98（95%CI，0.90至1.07）、1.16（95%CI，0.97至1.38）和1.07（95%CI，1.00至1.14）。没有证据表明存在效应修正。
这项大型个体患者数据荟萃分析的结果不支持HFE基因突变与冠心病或急性心肌梗死风险增加相关的观点。
