title: TNF polymorphisms are associated with toxic but not with aGVHD complications in the recipients of allogeneic sibling haematopoietic stem cell transplantation.
abstract: NcoI polymorphism within the promoter/enhancer region of TNFalpha and the first intron of TNFbeta encoding gene was analysed in 70 patients with haematological malignancies transplanted from HLA-identical sibling donors. The control group was composed of 130 healthy individuals. We showed that patients heterozygous for one or both TNF genes suffered more frequently from severe (grades III-IV) toxic complications than those carrying the other TNF genotypes (TNFA(*)1,2: 9/10 vs 30/60, P<0.05; TNFB(*)1,2: 20/26 vs 19/44, P<0.01; TNFA(*)1,2 TNFB(*)1,2: 9/9 vs 30/61, P<0.005). Conversely, patients having TNFB(*)2,2 less frequently presented with severe toxic lesions (17/39 vs 22/31, P<0.05). Additional analyses showed that TNFA(*)1,2, independent of the TNFB genotype composition, influenced the manifestation of grades III-IV toxic lesions, while TNFB(*)2,2 and TNFA(*)1,1 in combined association played a protective role. Logistic regression analysis confirmed the association of recipient TNFA(*)1,2 genotype with severe toxic complications, in addition to aggressive myeloablative conditioning regimen and female to male transplantation. No relation was found between TNF polymorphic features and aGvHD incidence by either uni- or multivariable analyses.
authors.affiliation: L Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Bogunia-Kubik
authors.forename: M
authors.initials: M
authors.lastname: Polak
authors.forename: A
authors.initials: A
authors.lastname: Lange
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000633:toxicity*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D005838:Genotype; D006086:Graft vs Host Disease / Q000209:etiology / Q000235:genetics*; D019337:Hematologic Neoplasms / Q000150:complications / Q000235:genetics / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007438:Introns / Q000235:genetics; D008233:Lymphotoxin-alpha / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D012044:Regression Analysis; D012307:Risk Factors; D012737:Sex Factors; D035781:Siblings; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha