Panigrahi Inusha, Agarwal Sarita
Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh-12, India.
Hematology. 2008 Aug;13(4):247-52. doi: 10.1179/102453308X316031.
Modifier genes are defined as inherited genetic variation that leads to a qualitative or quantitative difference in disease phenotype. This has made the prediction of the phenotype based upon the genotype more difficult. Beta-thalassemia phenotype is modified by co-existent other genetic alterations. Changes alpha/beta-globin ratio can either ameliorate the disease phenotype or increase the severity of the disease in beta-thalassemia. Primary modifiers primarily affecting the clinical presentation include alpha gene changes, XmnI polymorphism and hereditary persistence of fetal hemoglobin (HPFH) variants. 'Thalassemia intermedia' is a heterogenous group with interplay of several genetic factors. The nature of the beta-genotype as well as the knowledge of the presence or absence of alleviating factors help the physician to decide on commencement of a regular transfusion regime or other lines of management including hydroxyurea therapy. The secondary modifiers affect the severity of jaundice, bone disease, cardiac and thrombotic complications. The present review gives a concise discussion of various modifying genes and the influence on the phenotype of beta-thalassemia.
修饰基因被定义为导致疾病表型出现定性或定量差异的遗传变异。这使得基于基因型预测表型变得更加困难。β地中海贫血的表型会受到同时存在的其他基因改变的影响。α/β珠蛋白比例的变化既可以改善疾病表型，也可以增加β地中海贫血的疾病严重程度。主要影响临床表现的主要修饰因子包括α基因变化、XmnI多态性和胎儿血红蛋白（HPFH）变体的遗传性持续存在。“中间型地中海贫血”是一个由多种遗传因素相互作用形成的异质性群体。β基因型的性质以及是否存在缓解因素的信息有助于医生决定是否开始常规输血方案或其他治疗方法，包括羟基脲治疗。次要修饰因子会影响黄疸、骨骼疾病、心脏和血栓并发症的严重程度。本综述简要讨论了各种修饰基因及其对β地中海贫血表型的影响。
