Ellervik Christina, Birgens Henrik, Tybjaerg-Hansen Anne, Nordestgaard Børge G
Department of Clinical Biochemistry, Herlev University Hospital, Denmark.
Hepatology. 2007 Oct;46(4):1071-80. doi: 10.1002/hep.21885.
Hemochromatosis genotypes have been associated with liver disease, diabetes mellitus, heart disease, arthritis, porphyria cutanea tarda, stroke, neurodegenerative disorders, cancer, and venous disease. We performed meta-analyses including 202 studies with 66,263 cases and 226,515 controls to examine associations between hemochromatosis genotypes C282Y/C282Y, C282Y/H63D, C282Y/wild type, H63D/H63D, and H63D/wild type versus wild type/wild type and 9 overall endpoints and 22 endpoint subgroups. We also explored potential sources of heterogeneity. For liver disease, the odds ratio for C282Y/C282Y versus wild type/wild type was 3.9 (99% confidence interval: 1.9-8.1) overall, 11 (3.7-34) for hepatocellular carcinoma, 4.1 (1.2-14) for hepatitis C, and 10 (2.1-53) for nonalcoholic steatohepatitis. For porphyria cutanea tarda, the odds ratios were 48 (24-95) for C282Y/C282Y, 8.1 (3.9-17) for C282Y/H63D, 3.6 (1.8-7.3) for C282Y/wild type, 3.0 (1.6-5.6) for H63D/H63D, and 1.7 (1.0-3.1) for H63D/wild type versus wild type/wild type. Finally, for amyotrophic lateral sclerosis, the odds ratio was 3.9 (1.2-13) for H63D/H63D versus wild type/wild type. These findings were consistent across individual studies. The hemochromatosis genotypes were not associated with risk for diabetes mellitus, heart disease, arthritis, stroke, cancer, or venous disease in the overall analyses; however, the odds ratio for C282Y/C282Y versus wild type/wild type was 3.4 (1.1-11) for diabetes mellitus among North Europeans.
In aggregate, clinically ascertained cases who are homozygous for the C282Y mutation are associated with a 4-11-fold risk of liver disease, whereas all 5 hemochromatosis genotypes are associated with a 2-48-fold risk of porphyria cutanea tarda, and H63D/H63D is associated with a 4-fold risk of amyotrophic lateral sclerosis. These results, mainly from case-control studies, cannot necessarily be extrapolated to the general population.
血色素沉着症基因型与肝病、糖尿病、心脏病、关节炎、迟发性皮肤卟啉症、中风、神经退行性疾病、癌症和静脉疾病有关。我们进行了荟萃分析，纳入202项研究，共66263例病例和226515例对照，以检验血色素沉着症基因型C282Y/C282Y、C282Y/H63D、C282Y/野生型、H63D/H63D和H63D/野生型与野生型/野生型相比，与9个总体终点和22个终点亚组之间的关联。我们还探讨了异质性的潜在来源。对于肝病，C282Y/C282Y与野生型/野生型相比的总体比值比为3.9（99%置信区间：1.9 - 8.1），肝细胞癌为11（3.7 - 34），丙型肝炎为4.1（1.2 - 14），非酒精性脂肪性肝炎为10（2.1 - 53）。对于迟发性皮肤卟啉症，C282Y/C282Y的比值比为48（24 - 95），C282Y/H63D为8.1（3.9 - 17），C282Y/野生型为3.6（1.8 - 7.3），H63D/H63D为3.0（1.6 - 5.6），H63D/野生型与野生型/野生型相比为1.7（1.0 - 3.1）。最后，对于肌萎缩侧索硬化症，H63D/H63D与野生型/野生型相比的比值比为3.9（1.2 - 13）。这些发现在各个研究中是一致的。在总体分析中，血色素沉着症基因型与糖尿病、心脏病、关节炎、中风、癌症或静脉疾病的风险无关；然而，在北欧人中，C282Y/C282Y与野生型/野生型相比，糖尿病的比值比为3.4（1.1 - 11）。
总体而言，临床确诊的C282Y突变纯合子病例患肝病的风险增加4至11倍，而所有5种血色素沉着症基因型患迟发性皮肤卟啉症的风险增加2至48倍，H63D/H63D患肌萎缩侧索硬化症的风险增加4倍。这些主要来自病例对照研究的结果不一定能外推至普通人群。
