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  • Title: Investigation of TNF-alpha, TGF-beta 1, IL-10, IL-6, IFN-gamma, MBL, GPIA, and IL1A gene polymorphisms in patients with idiopathic thrombocytopenic purpura.
    Author: Pehlivan M, Okan V, Sever T, Balci SO, Yilmaz M, Babacan T, Pehlıvan S.
    Journal: Platelets; 2011; 22(8):588-95. PubMed ID: 21591983.
    Abstract:
    Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by the presence of autoantibodies developing against thrombocyte membrane glycoproteins (GPs), such as GPIIa/IIIa and GPIb/IX. Single nucleotide polymorphisms (SNPs) of inflammatory cytokine genes were investigated in 71 patients with chronic ITP and 71 healthy controls, and they were compared with the clinical parameters. The polymorphisms in the SNPs were investigated with the polymerase chain reaction, polymerase chain reaction with sequence specific primer, and polymerase chain reaction-restriction fragment length polymorphism methods. It was found that the high expression of TNF-alpha (-308) AG phenotype significantly increased in cases with ITP (odds ratio, OR: 0.318, 95% confidence intervals, CI: 0.103-0.987, p < 0.05). TT genotype in TGF-beta 1 (codon 10) significantly decreased in ITP in comparison with the controls (OR: 0.342, 95% CI: 0.149-0.787, p = 0.016). IFN-gamma (+874) TT genotype was detected to be high in cases with ITP (OR: 3.301, 95% CI: 1.400-7.784, p < 0.05), whereas AA genotype was found to be significantly lower (OR: 4.993, 95% CI: 1.586-15.721, p < 0.05). MBL (codon 54) BB genotype (OR: 1.164, 95% CI: 1.059-1.279, p < 0.05) and IL1A A1/A2 genotype (OR: 0.249, 95% CI: 0.076-0.815, p < 0.05) were found to be significantly higher in cases with ITP than in healthy controls. TNF-alpha (-308) AG phenotype was detected to be significantly higher in steroid-refractory and splenectomized cases at the end of the first year than in the steroid-responsive (complete response (CR) and remission (R)) cases (OR: 4.137, 95% CI: 1.156-14.807, p < 0.05). When we compared the cases, from whom we obtained a CR at their first steroid response, with 12 cases, who entered R but from whom we could not obtain any CR, the frequencies of IFN-gamma (+874) AA genotype were found as 12 (20.3%) and 6 (50%) (OR: 0.082, 95% CI: 0.009-0.793, p < 0.05). MBL (codon 54) AB genotype was detected to be significantly higher in CR patients than in R cases (OR: 1.273, 95% CI: 1.110-1.459, p < 0.05). With these findings, it was found that TNF-alpha/AG, TGF-beta 1/TT, IFN-gamma/TT, MBL/BB, and IL-1RA A1/A2 genotypes were detected as the genes of susceptibility to ITP, while TNF-alpha/AG, IFN-gamma/AA, and MBL/AB genotypes might be important in response to steroid treatment.
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