Department of Hematology, School of Medicine, Gaziantep University, Turkey.
Platelets. 2011;22(8):588-95. doi: 10.3109/09537104.2011.577255. Epub 2011 May 19.
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.
免疫性血小板减少性紫癜（ITP）是一种自身免疫性疾病，其特征是存在针对血小板膜糖蛋白（GPs）的自身抗体，如 GPIIa/IIIa 和 GPIb/IX。在 71 例慢性 ITP 患者和 71 名健康对照者中研究了炎症细胞因子基因的单核苷酸多态性（SNP），并将其与临床参数进行了比较。采用聚合酶链反应、聚合酶链反应与序列特异性引物、聚合酶链反应-限制性片段长度多态性方法检测 SNP 的多态性。结果发现，ITP 患者 TNF-α（-308）AG 表型的高表达明显增加（比值比，OR：0.318，95%置信区间，CI：0.103-0.987，p<0.05）。与对照组相比，TGF-β1（密码子 10）TT 基因型在 ITP 中显著降低（OR：0.342，95%CI：0.149-0.787，p=0.016）。IFN-γ（+874）TT 基因型在 ITP 患者中检测到较高（OR：3.301，95%CI：1.400-7.784，p<0.05），而 AA 基因型则显著降低（OR：4.993，95%CI：1.586-15.721，p<0.05）。MBL（密码子 54）BB 基因型（OR：1.164，95%CI：1.059-1.279，p<0.05）和 IL1A A1/A2 基因型（OR：0.249，95%CI：0.076-0.815，p<0.05）在 ITP 患者中明显高于健康对照组。在第一年结束时，类固醇难治性和脾切除患者的 TNF-α（-308）AG 表型明显高于类固醇反应性（完全反应（CR）和缓解（R））患者（OR：4.137，95%CI：1.156-14.807，p<0.05）。当我们比较那些在第一次类固醇反应中获得 CR 的患者与 12 例进入 R 但无法获得任何 CR 的患者时，发现 IFN-γ（+874）AA 基因型的频率分别为 12（20.3%）和 6（50%）（OR：0.082，95%CI：0.009-0.793，p<0.05）。CR 患者的 MBL（密码子 54）AB 基因型明显高于 R 例（OR：1.273，95%CI：1.110-1.459，p<0.05）。有了这些发现，我们发现 TNF-α/AG、TGF-β1/TT、IFN-γ/TT、MBL/BB 和 IL-1RA A1/A2 基因型被认为是 ITP 的易感基因，而 TNF-α/AG、IFN-γ/AA 和 MBL/AB 基因型可能在类固醇治疗反应中很重要。
