Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Begumpet, Hyderabad, India.
Eur J Haematol. 2011 Jun;86(6):502-6. doi: 10.1111/j.1600-0609.2011.01614.x.
The inherited disorders of hemoglobin synthesis are the most common monogenic disorders worldwide. They include thalassemias, hemoglobin variants, and hereditary persistence of fetal hemoglobin. β-thalassemia is the most common monogenic disorder in India. Clinical manifestations of β-thalassemia are extremely variable in severity. The reasons for this heterogeneity are not very well understood. Previous studies have shown that the genetic variants that modulate HbF levels have a very strong impact on ameliorating the clinical phenotype. In the present study, 5570 blood samples from suspected cases were analyzed using HPLC, amplification refractory mutation system-PCR and reverse dot blot techniques. Of 5570 individuals, we found 676 cases of β-thalassemia disease. Molecular analysis revealed the presence of different β-thalassemia mutations in the population under study. Patients with β-thalassemia were classified into mild, moderate, and severe according to severity score based on Hb level, age of onset, age at which patients received their first blood transfusion, degree of growth retardation and splenectomy. Patients with β-thalassemia were analyzed for zinc finger and homeoboxes 2 (ZHX2) G779A polymorphism, and the association between ZHX2 gene polymorphism and severity of β-thalassemia was evaluated. We did not find a significant difference in genotypic and allelic frequency of ZHX2 gene between mild and moderate, mild and severe, and moderate and severe cases. There was no significant difference in high and low percentage of HbF in GG, GA, and AA bearing individuals showing that ZHX2 gene variant has no role in ameliorating the severity of β-thalassemia major in the South Indian population from Andhra Pradesh.
血红蛋白合成遗传障碍是全球最常见的单基因疾病。它们包括地中海贫血、血红蛋白变体和胎儿血红蛋白持续存在。β-地中海贫血是印度最常见的单基因疾病。β-地中海贫血的临床表现严重程度差异极大。造成这种异质性的原因还不是很清楚。先前的研究表明，调节 HbF 水平的遗传变异对改善临床表型有很强的影响。在本研究中，使用 HPLC、扩增障碍突变系统-PCR 和反向斑点印迹技术分析了 5570 份疑似病例的血液样本。在 5570 个人中，我们发现了 676 例β-地中海贫血疾病。分子分析显示，在所研究的人群中存在不同的β-地中海贫血突变。根据基于 Hb 水平、发病年龄、首次输血年龄、生长迟缓程度和脾切除术的严重程度评分，将β-地中海贫血患者分为轻度、中度和重度。对β-地中海贫血患者进行锌指和同源盒 2（ZHX2）G779A 多态性分析，并评估 ZHX2 基因多态性与β-地中海贫血严重程度的关系。我们没有发现 ZHX2 基因在轻度和中度、轻度和重度以及中度和重度病例之间的基因型和等位基因频率存在显著差异。在 GG、GA 和 AA 个体中，HbF 高百分比和低百分比之间没有显著差异，表明 ZHX2 基因变异在改善安得拉邦南印度人群β-地中海贫血严重程度方面没有作用。
