Association of vitamin D receptor polymorphisms with the outcome of allogeneic haematopoietic stem cell transplantation.
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.
Bogunia-Kubik
K
K
Department of Clinical Immunology, L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland. bogunia@iitd.pan.wroc.pl
Middleton
P
P
Norden
J
J
Dickinson
A
A
Lange
A
A
D000293:Adolescent; D000328:Adult; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006086:Graft vs Host Disease / Q000235:genetics* / Q000401:mortality; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D018167:Receptors, Calcitriol / Q000235:genetics*; D016896:Treatment Outcome
D018167:Receptors, Calcitriol