Bogunia-Kubik K, Middleton P, Norden J, Dickinson A, Lange A
Department of Clinical Immunology, L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
Int J Immunogenet. 2008 Jun;35(3):207-13. doi: 10.1111/j.1744-313X.2008.00758.x. Epub 2008 Feb 28.
Recently, vitamin D receptor (VDR) polymorphism has been identified as an additional genetic factor associated with the outcome after allogeneic haematopoietic stem cell transplantation (HSCT) from HLA-matched sibling donors. In the present study, VDR ApaI, TaqI and FokI alleles were typed using single strand conformation polymorphism in 123 Polish recipients and their sibling or alternative donors to test the associations of VDR polymorphisms with HSCT outcome. Four VDR genotypes were identified as risk factors of acute graft-versus-host disease (aGVHD). Donor ApaI AA (OR = 7.245, P = 0.009), source of HSC (OR = 7.001, P = 0.007), transplantation from an alternative donor (OR = 6.630, P = 0.007) and donor FokI FF (OR = 4.473, P = 0.025) significantly contributed to the development of grades II-IV aGVHD, while recipient ApaI aa (OR = 3.233, P = 0.069), recipient FokI FF (OR = 2.558, P = 0.077) and female to male transplants (OR = 2.955, P = 0.099) were found to be less significant factors. In addition, the presence of ApaI aa genotype in the recipient was found to be associated with increased likelihood of death (P = 0.0228). The present study contributes to the studies demonstrating a role of VDR polymorphisms in HSCT outcome. In addition to previously described correlations of ApaI a allele and occurrence of severe grades III-IV aGVHD and (linked with ApaI aa) recipient TaqI TT genotype with aGVHD, the novel associations of recipient and donor FokI FF genotype and the increased aGVHD risk and recipient ApaI aa with survival were identified.
最近，维生素D受体（VDR）多态性已被确定为与来自HLA匹配同胞供者的异基因造血干细胞移植（HSCT）后结局相关的另一个遗传因素。在本研究中，采用单链构象多态性对123名波兰受者及其同胞或替代供者的VDR ApaI、TaqI和FokI等位基因进行分型，以检测VDR多态性与HSCT结局的相关性。四种VDR基因型被确定为急性移植物抗宿主病（aGVHD）的危险因素。供者ApaI AA（比值比[OR]=7.245，P=0.009）、造血干细胞来源（OR=7.001，P=0.007）、来自替代供者的移植（OR=6.630，P=0.007）和供者FokI FF（OR=4.473，P=0.025）对II-IV级aGVHD的发生有显著影响，而受者ApaI aa（OR=3.233，P=0.069）、受者FokI FF（OR=2.558，P=0.077）和女性对男性移植（OR=2.955，P=0.099）则是不太显著的因素。此外，发现受者中存在ApaI aa基因型与死亡可能性增加相关（P=0.0228）。本研究有助于证明VDR多态性在HSCT结局中作用的研究。除了先前描述的ApaI a等位基因与严重III-IV级aGVHD的发生以及（与ApaI aa相关）受者TaqI TT基因型与aGVHD的相关性外，还发现了受者和供者FokI FF基因型与aGVHD风险增加以及受者ApaI aa与生存的新关联。
