HSP70-hom gene polymorphism in allogeneic hematopoietic stem-cell transplant recipients correlates with the development of acute graft-versus-host disease.
BACKGROUND
A number of genetic polymorphisms have been shown to be associated with the outcome after allogeneic hematopoietic stem-cell transplantation (HSCT). In the present study, HSP70-hom polymorphism (+2763 G/A) was analyzed in the patients and donors of allogeneic HSCT in relation to transplantation outcome, susceptibility for generation of severe toxic lesions, and acute (a) graft-versus-host disease (GVHD).


METHODS
One hundred thirty-three recipients of allogeneic hematopoietic stem cells and 64 haploidentical and matched unrelated donors were investigated. All these individuals were typed for dimorphism within the HSP70-hom gene (+2763 G/A) with the use of amplification refractory mutation system technique. RESULTS.: Patients with the HSP-AA homozygous genotype presented more frequently with grade II to IV toxic lesions (12 of 14 vs. 61 of 105, P = 0.039) and aGVHD (12 of 16 vs. 56 of 114, P = 0.045). Conversely, DRB1*11 was associated with a lower risk of aGVHD manifestation (10 of 31 vs. 58 of 99, P = 0.009). These contrary associations of HSP-AA and DRB1*11 with the risk of aGVHD were confirmed using logistic regression modeling in multivariable analysis (HSP-AA, odds ratio [OR] = 3.833, P = 0.004; DRB1*11, OR = 0.224, P = 0.048). None of donor HSP genotypes or patient-donor incompatibility within HSP alleles was associated with susceptibility to toxic complications or aGVHD.


CONCLUSIONS
Polymorphism of the HSP70-hom gene is associated with the development of posttransplant complications. Recipient HSP-AA homozygous genotype is a risk factor for aGVHD.
Bogunia-Kubik
Katarzyna
K
Department of Clinical Immunology, L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolf Weigl 12, 53-114 Wroclaw, Poland. bogunia@iitd.pan.wroc.pl
Lange
Andrzej
A
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D046148:Donor Selection; D005260:Female; D005838:Genotype; D006086:Graft vs Host Disease / Q000235:genetics* / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology; D059811:HLA-DRB1 Chains; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D018380:Hematopoietic Stem Cell Transplantation; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors; D014180:Transplantation; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D018840:HSP70 Heat-Shock Proteins