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Polymorphism of the tumour necrosis factor‐alpha and lymphotoxin‐alpha genes in chronic lymphocytic leukaemia
Author(s) -
Demeter Judith,
Porzsolt Franz,
Rämisch Stephanie,
Schmidt Dorothee,
Schmid Mathias,
Messer Gerald
Publication year - 1997
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1997.9912636.x
Subject(s) - lymphotoxin alpha , lymphotoxin , lymphotoxin beta receptor , alpha (finance) , tumor necrosis factor alpha , immunology , medicine , gene , cancer research , biology , genetics , construct validity , nursing , patient satisfaction
The neoplastic cells of CLL are able to produce TNF which is known to stimulate the proliferation of CLL cells in an autocrine and paracrine manner. Genetic polymorphism of molecules of the TNF ligand superfamily has been described and certain alleles were suspected to predispose to variant biological responses. Previously, the rare allele TNFB*1 of the TNF‐β/lymphotoxin (LT)‐α gene (NcoI, asparagine at amino acid position 26) was found to be associated with a stronger LT‐α response of PBMC in vitro . We now report on a significant increase of the allele TNF1 (TNFA −308 G) of the TNF‐α promoter/enhancer polymorphism in a group of 73 CLL patients when compared to healthy individuals (RR=3.18, 95% confidence interval 1.57–8.3; P =0.006). The allelic distribution of the TNF‐β/LT‐α NcoI polymorphism did not differ significantly from randomized healthy controls. On the other hand, the frequency of the allele TNFB*2 was increased in CLL patients with advanced clinical stage ( P =0.0004). These findings indicate immunogenetic associations involving polymorphisms of cytokine genes serving as paracrine and autocrine growth factors, which thus can contribute to the pathogenesis of the TNF/LT‐sensitive haematological malignancy CLL.