Van Den Eede Filip, Venken Tine, Del-Favero Jurgen, Norrback Karl-Fredrik, Souery Daniel, Nilsson Lars Göran, Van den Bossche Bart, Hulstijn Wouter, Sabbe Bernard G C, Cosyns Paul, Mendlewicz Julien, Adolfsson Rolf, Van Broeckhoven Christine, Claes Stephan J
Department of Molecular Genetics VIB8, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium.
Psychiatry Res. 2007 Sep 30;153(1):17-25. doi: 10.1016/j.psychres.2006.12.018. Epub 2007 Jun 28.
Corticotropin-releasing factor-binding protein (CRF-BP) regulates the availability of free CRF and is a functional candidate gene for affective disorders. Previous research showed an association between polymorphisms in the CRF-BP gene and recurrent major depression (MDD) in a Swedish sample. The purpose of the current study was to re-evaluate the previous findings in an extended Swedish sample and in an independent Belgian sample of patients with recurrent MDD and in control samples. In total, 317 patients and 696 control individuals were included. Five single nucleotide polymorphisms (SNPs) and a deletion polymorphism in the CRF-BP gene were genotyped and the haplotype block structure of the gene was assessed. In the extended Swedish population, there was a trend towards an association between two SNPs and MDD. The subsequent gender analysis showed significant associations of three SNPs (CRF-BPs2 T; CRF-BPs11 T and CRF-BPs12 C) and haplotype G_T_C_T_C with MDD in Swedish males. However, these findings did not withstand correction for multiple testing and there were no significant SNP or haplotype associations in the Belgian MDD sample. In conclusion, this study does not provide confirmatory evidence for a role of the CRF-BP gene in the vulnerability for MDD in general. The association between genetic CRF-BP variants and MDD may be sexually dimorphic, but this issue requires further investigation in a larger sample.
促肾上腺皮质激素释放因子结合蛋白（CRF-BP）调节游离CRF的可用性，是情感障碍的一个功能性候选基因。先前的研究表明，在瑞典样本中，CRF-BP基因多态性与复发性重度抑郁症（MDD）之间存在关联。本研究的目的是在一个扩大的瑞典样本、一个独立的比利时复发性MDD患者样本以及对照样本中重新评估先前的研究结果。总共纳入了317例患者和696名对照个体。对CRF-BP基因中的五个单核苷酸多态性（SNP）和一个缺失多态性进行了基因分型，并评估了该基因的单倍型模块结构。在扩大的瑞典人群中，两个SNP与MDD之间存在关联趋势。随后的性别分析显示，在瑞典男性中，三个SNP（CRF-BPs2 T；CRF-BPs11 T和CRF-BPs12 C）以及单倍型G_T_C_T_C与MDD存在显著关联。然而，这些发现无法经受多重检验的校正，并且在比利时MDD样本中没有显著的SNP或单倍型关联。总之，本研究没有为CRF-BP基因在MDD易感性中的作用提供确证性证据。遗传性CRF-BP变异与MDD之间的关联可能存在性别差异，但这个问题需要在更大的样本中进一步研究。
