Institute of Human Genetics, MRI, Technische Universität München, Munich, Germany.
Hum Mol Genet. 2011 Mar 1;20(5):1042-7. doi: 10.1093/hmg/ddq538. Epub 2010 Dec 10.
The level of body iron storage and the erythropoietic need for iron are indicated by the serum levels of ferritin and soluble transferrin receptor (sTfR), respectively. A meta-analysis of five genome-wide association studies on sTfR and ferritin revealed novel association to the PCSK7 and TMPRSS6 loci for sTfR and the HFE locus for both parameters. The PCSK7 association was the most significant (rs236918, P = 1.1 × 10E-27) suggesting that proprotein convertase 7, the gene product of PCSK7, may be involved in sTfR generation and/or iron homeostasis. Conditioning the sTfR analyses on transferrin saturation abolished the HFE signal and substantially diminished the TMPRSS6 signal while the PCSK7 association was unaffected, suggesting that the former may be mediated by transferrin saturation whereas the PCSK7-associated effect on sTfR generation appears to be more direct.
分别通过血清铁蛋白和可溶性转铁蛋白受体（sTfR）水平来指示体内铁储存水平和对铁的红细胞生成需求。对五项关于 sTfR 和铁蛋白的全基因组关联研究进行的荟萃分析揭示了与 sTfR 的 PCSK7 和 TMPRSS6 基因座以及这两个参数的 HFE 基因座的新关联。PCSK7 关联最为显著（rs236918，P=1.1×10E-27），表明前蛋白转化酶 7（PCSK7 的基因产物）可能参与 sTfR 的生成和/或铁稳态。sTfR 分析条件化后，HFE 信号被消除，TMPRSS6 信号大大减弱，而 PCSK7 关联不受影响，这表明前者可能通过转铁蛋白饱和度介导，而 PCSK7 对 sTfR 生成的影响似乎更为直接。
