Bahrami Zadegan Sobhan, Mousavi Sayed H, Damavandi Narges, Samiee Aref Mohammad H, Zeinali Sirous
Department of Biotechnology, College of Science, University of Tehran.
Dr Zeinali's Medical Genetics Laboratory, Kawsar Human Genetics Research Center, Tehran, Iran.
Blood Coagul Fibrinolysis. 2020 Jan;31(1):11-15. doi: 10.1097/MBC.0000000000000860.
: Development of alloantibodies against factor VIII (FVIII) in patients with severe hemophilia A is the main complication of FVIII replacement therapy. There are many studies indicating several genetic factors associated with inhibitor development. A recent study showed that there is a correlation between the risk of inhibitor development and LCT rs3754689 polymorphism among Italian hemophilia A patients. The aim of this study was to speculate whether LCT rs3754689 polymorphism is correlated to inhibitor development in Afghan and Iranian patients. In addition, we assessed the association of F8 gene mutations and inhibitor development in Iranian patients. This case-control study was conducted on 33 severe hemophilia A patients with inhibitor and 119 samples without inhibitor. Genotyping was performed by Sanger sequencing, inverse and multiplex PCR. According to the obtained data, we found a significant correlation between LCT rs3754689 polymorphism and the risk of inhibitor development in Afghan patients (observed risk, 0.11; 95% confidence interval, 0.01-0.88; P = 0.012). Among Iranian patients, rs3754689 polymorphism showed no significant association with inhibitor development against FVIII (P > 0.05). However, we found a significant correlation between the risk of inhibitor formation and large deletions and nonsense mutations in F8 gene among Iranian patients (observed risk, 7.25; 95% confidence interval, 1.93-27.18; P = 0.003). Lack of association of rs3754689 polymorphism in Iranian population shows the various effects of genetic markers in different populations. More studies in different ethnicities or larger sample sizes are recommended.
在重度甲型血友病患者中，针对凝血因子VIII（FVIII）产生同种抗体是FVIII替代疗法的主要并发症。许多研究表明了与抑制剂形成相关的几个遗传因素。最近一项研究显示，在意大利甲型血友病患者中，抑制剂形成风险与LCT rs3754689多态性之间存在相关性。本研究的目的是推测LCT rs3754689多态性在阿富汗和伊朗患者中是否与抑制剂形成相关。此外，我们评估了伊朗患者中F8基因突变与抑制剂形成之间的关联。本病例对照研究针对33例有抑制剂的重度甲型血友病患者和119例无抑制剂的样本进行。通过桑格测序、反向和多重PCR进行基因分型。根据获得的数据，我们发现LCT rs3754689多态性与阿富汗患者抑制剂形成风险之间存在显著相关性（观察到的风险，0.11；95%置信区间，0.01 - 0.88；P = 0.012）。在伊朗患者中，rs3754689多态性与针对FVIII的抑制剂形成无显著关联（P > 0.05）。然而，我们发现伊朗患者中抑制剂形成风险与F8基因的大片段缺失和无义突变之间存在显著相关性（观察到的风险，7.25；95%置信区间，1.93 - 27.18；P = 0.003）。伊朗人群中rs3754689多态性缺乏关联表明遗传标记在不同人群中有不同影响。建议在不同种族中进行更多研究或采用更大样本量。
