Rehman Sadia, Ahmed Parvez, Saba Nusrat, Munir Saeeda, Sajjad Sumaira, Satti Tariq Mehmood, Chaudary Qamar-un-Nisa, Mansoor Atika
Institute of Biomedical and Genetic Engineering Islamabad, G9/1 Mauve Area, Islamabad, 44000, Pakistan.
Armed Forces Institute of Bone Marrow Transplantation Centre, Rawalpindi, Pakistan.
Ann Hematol. 2015 Dec;94(12):1965-71. doi: 10.1007/s00277-015-2482-0. Epub 2015 Sep 1.
Interaction of environmental and genetic elements plays a vital role in the pathogenesis of aplastic anemia (AA). Glutathione S-transferase (GST) is a key detoxifying enzyme. Absence or low levels of this enzyme may genetically predispose individuals to AA. GST genes GSTM1 and GSTT1 are polymorphic. The aim of this study was to screen Pakistani AA patients and controls for GSTM1 deletion GSTM0 and GSTT1 deletion GSTT0 and perform meta-analysis using our data and other published data regarding these polymorphisms. DNA samples from 137 patients and 220 controls were screened using multiplex polymerase chain reaction. GSTM0 emerged as susceptible genotype for AA in Pakistan with a percentage frequency of 49.6 % as compared to 30 % in controls with odds ratio (OR) of 2.25, 95 % confidence interval (CI) of 1.4-3.5 and corrected p = 0.006. The meta-analysis showed a significant association between the null genotype GSTT0 and AA in overall analysis with OR of 1.47, 95 % CI of 1.01-2.13 and p value of 0.04 in random effects model. Studies like these could play a role in understanding the underlying path in AA pathogenesis and therefore can help in designing means for prevention, diagnose and treatment.
环境因素与遗传因素的相互作用在再生障碍性贫血（AA）的发病机制中起着至关重要的作用。谷胱甘肽S-转移酶（GST）是一种关键的解毒酶。该酶的缺失或低水平可能使个体在遗传上易患AA。GST基因GSTM1和GSTT1具有多态性。本研究的目的是对巴基斯坦AA患者和对照组进行GSTM1缺失（GSTM0）和GSTT1缺失（GSTT0）筛查，并利用我们的数据以及其他已发表的关于这些多态性的数据进行荟萃分析。使用多重聚合酶链反应对137例患者和220例对照的DNA样本进行筛查。在巴基斯坦，GSTM0成为AA的易感基因型，其百分比频率为49.6%，而对照组为30%，优势比（OR）为2.25，95%置信区间（CI）为1.4 - 3.5，校正p = 0.006。荟萃分析显示，在总体分析中，无效基因型GSTT0与AA之间存在显著关联，随机效应模型中的OR为1.47，95%CI为1.01 - 2.13，p值为0.04。此类研究有助于理解AA发病机制的潜在途径，从而有助于设计预防、诊断和治疗方法。
