Immune regulatory gene polymorphisms as predisposing risk factors for the development of factor VIII inhibitors in Indian severe haemophilia A patients
Immune regulatory gene polymorphisms as predisposing risk factors for the development of factor VIII inhibitors in Indian severe haemophilia A patients
复制标题
免疫调节基因多态性是印度严重甲型血友病患者产生因子 VIII 抑制剂的易感危险因素
作者：
P. Pinto;Kanjaksha Ghosh;S. Shetty
血友病A患者替代治疗的严重并发症是凝血因子VIII的抑制剂的开发，导致出血、发病率和死亡率的增加。目前还没有关于印度严重血友病A患者中抑制物形成的危险因素的数据。我们的目的是研究免疫调节基因多态性在抑制物形成中的作用。应用聚合酶链式反应-限制性片段长度多态性、测序和等位基因特异性聚合酶链式反应对50例甲型重型血友病患者和70例甲型重型血友病患者的14个免疫调节基因β、IL 4、IL 10、TnFA和CTLA4进行了分析。在抑制剂阳性患者中，IL10启动子‘GCC’单倍型(P：0.002，OR：3.452，95%CI：1.607-7.416)和‘GCC/ATA’(P：0.011，OR：3.492，95%CI：1.402-8.696)单倍型与高和中等IL-10产量相关的总体显著高于非GCC单倍型(P：0.002，OR：0.290，在抑制物阴性患者中，与IL10合成低下相关的95%CI为0.135~0.622)和‘ATA/ATA’单倍型(P：0.025，OR：0.278，95%CI：0.096~0.802)显著高于对照组。在抑制物阳性组中，TNFArs1799724C/T杂合子的发生率显著高于对照组(P：0.021，OR：3.190，95%CI：1.273~7.990)，而其他多态与抑制物的存在无统计学意义。不同的免疫调节基因多态性可能是严重血友病A患者产生抑制物的危险因素。
Development of inhibitors to factor VIII, a serious complication of replacement therapy in haemophilia A patients, leads to increased bleeding, morbidity and mortality. There is no data on the risk factors for inhibitor development in Indian patients with severe haemophilia A. Our aim was to study the role of immune regulatory gene polymorphisms in the development of inhibitors. Fourteen immune regulatory gene polymorphisms (IL1β, IL4, IL10, TNFA and CTLA4) were analysed in 120 patients with severe haemophilia A, i.e. 50 inhibitor positive patients, and 70 inhibitor negative control patients, by PCR‐RFLP, DNA sequencing and allele‐specific PCRs. The IL10 promoter ‘GCC’ haplotypes overall (P: 0.002, OR: 3.452, 95% CI: 1.607–7.416), and ‘GCC/ATA’ (P: 0.011, OR: 3.492, 95% CI: 1.402–8.696) haplotype, associated with high and intermediate IL10 production, respectively, were significantly higher in inhibitor positive patients, whereas the ‘non‐GCC’ haplotypes overall (P: 0.002,OR: 0.290, 95% CI 0.135–0.622) and ‘ATA/ATA’ haplotype (P: 0.025, OR: 0.278, 95% CI: 0.096–0.802), associated with low IL10 synthesis, were significantly higher among inhibitor negative patients. The TNFA rs1799724 C/T heterozygote prevalence was significantly higher in the inhibitor positive group (P: 0.021, OR: 3.190, 95% CI: 1.273–7.990), whereas the other polymorphisms showed no statistically significant association with the presence of inhibitors. Different immune regulatory gene polymorphisms play a significant role as possible risk factors for the development of inhibitors in severe haemophilia A patients.
影响因子：
3.5
作者：
Marron, MP;Raffel, LJ;She, JX
通讯作者：
She, JX