3e2ae00d-8b54-4b23-8da0-a9bf942eeaf0
title
Single nucleotide polymorphisms of the inflammatory cytokine genes in adults with chronic immune thrombocytopenic purpura.
601e8809-4702-408e-918a-a5dee4430dde
abstract
Single nucleotide polymorphisms (SNPs) of inflammatory cytokine genes were examined in 84 adult Japanese patients with chronic immune thrombocytopenic purpura (ITP) and 56 race-matched healthy controls. The SNPs examined were within the genes encoding  tumour necrosis factor (TNF)-alpha  ( -238 G/A  and  -308 G/A ),  TNF-beta  ( +252 G/A ), and  interleukin (IL)-1beta  ( -511 C/T  and  +3953 T/C ). Of these SNPs, the frequency of the  TNF-beta   (+252) G/G  phenotype was significantly higher in ITP patients than in healthy controls (21% vs. 7%, P = 0.04, odds ratio = 3.6, 95% confidence interval 1.1-11.1), while no significant association was detected for the other SNPs. The distribution of the  TNF-beta  (+252) phenotype was not associated with human leucocyte antigen class II alleles or the therapeutic response in ITP patients. The frequency of circulating anti-glycoprotein IIb/IIIa antibody-producing B cells was significantly higher in ITP patients with the  TNF-beta   (+252) G/G  phenotype than in those with the G/A or A/A phenotype (11.9 +/- 4.9 vs. 6.8 +/- 4.9 and 3.7 +/- 2.8 per 10(5) peripheral blood mononuclear cells; P = 0.02 and P < 0.001, respectively). These findings suggest that the SNP located at  TNF-beta  (+252) contributes to susceptibility to chronic ITP by controlling the autoreactive B-cell responses to platelet membrane glycoproteins.