Clinical relevance of the TNF-alpha promoter/enhancer polymorphism in patients with aplastic anemia.
Immune-mediated inhibition of hematopoiesis has been suspected as a major cause of the suppressed growth of progenitor cells in aplastic anemia (AA). Overproduction of TNF-alpha by bone marrow and peripheral blood-derived cells was shown to be of pathogenetic importance. Genetic factors have been suggested by higher specific histocompatibility antigen frequencies among AA patients as a group and among those unresponsive to immunosuppressive therapy with cyclosporine. In the present work we expand on the evidence for the contribution of the TNF system to therapeutic responses in patients with AA. The response to immunosuppressive therapy at 3 months was found to be significantly more frequent among carriers of the TNF2 (TNF -308 A) gene (TNF2 homozygotes and heterozygotes of the TNF-alpha promoter/enhancer polymorphism) than among those patients not carrying the TNF2 gene. The allelic distribution of the LT-alpha (TNF-beta) NcoI and IL-1 receptor antagonist variable number tandem repeat (VNTR) polymorphisms did not differ among the subgroups of patients. The association of the TNF-alpha genotype with a response to immunosuppressive therapy points to an immunogenetic association that may contribute to the pathogenesis and therapeutic response of aplastic anemia.
Demeter
Judit
J
Department of Medicine III, University of Ulm, Ulm, Germany. demjud@bel1.sote.hu
Messer
Gerald
G
Schrezenmeier
Hubert
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D000741:Anemia, Aplastic / Q000188:drug therapy / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D004742:Enhancer Elements, Genetic / Q000235:genetics; D005787:Gene Frequency; D005838:Genotype; D005858:Germany; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D053590:Interleukin 1 Receptor Antagonist Protein; D008233:Lymphotoxin-alpha / Q000235:genetics; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D012795:Sialoglycoproteins / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
C507763:IL1RN protein, human; D007166:Immunosuppressive Agents; D053590:Interleukin 1 Receptor Antagonist Protein; D008233:Lymphotoxin-alpha; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha