OBJECTIVE: To investigate determinants contributing to the non-elevation of HbF expression in β0-thalassemia/HbE disease.
METHODS: We studied 231 patients with β0-thalassemia/HbE confirmed by DNA analysis; classified them into the low-HbF (n = 62) and high-HbF (n = 169) groups; analyzed hematological parameters and hemoglobin levels in both groups; and characterized mutations in β- and α-globin genes and genetic variants in γ-globin promoters.
RESULTS: Both groups showed similar rates of type β0-thalassemia mutations but significantly different proportions of α-globin mutations: approximately 88.7% (95% confidence interval [CI] = 66.8-115.5) and 39.1% (95% CI = 30.2-49.7) in the low- and high-HbF groups, respectively. The results revealed single-nucleotide polymorphisms (SNPs) at -158 (C>T) in the Gγ-globin promoters and novel SNPs at the 5\' untranslated region position 25 (G>A) in Aγ-globin promoters. The distribution of CC genotypes of the Gγ-globin promoter in the low-HbF group was significantly higher than that in the high-HbF group.
CONCLUSIONS: Cases with HbE predominance with low-HbF levels and undetectable HbA may not be as conclusive as those with homozygous HbE until DNA analysis is performed. Concomitant inheritance of α-thalassemia is an important inherent factor modifying HbF expression in a typical β0-thalassemia/HbE, and SNPs with the CC genotype in the Gγ-globin promoter may indicate unelevated HbF expression in patients with this disease.
目的:研究β0-地中海贫血/HbE病中HbF表达不升高的相关因素。
方法:我们研究了231例经DNA分析证实的β0-地中海贫血/HbE患者;将其分为低HbF组(n=62)和高HbF组(n=169);分析了两组的血液学参数和血红蛋白水平;并表征了β-和α-珠蛋白基因的突变以及γ-珠蛋白启动子的遗传变异。
结果:两组均显示出相似的β0型地中海贫血突变率,但α-珠蛋白突变的比例显着不同:在低和高HbF组中约为88.7%(95%置信区间[CI]=66.8-115.5)和39.1%(95%CI=30.2-49.7),分别。结果揭示了Gγ-珠蛋白启动子中-158(C>T)的单核苷酸多态性(SNP)和Aγ-珠蛋白启动子中5'非翻译区25位(G>A)的新SNP。低HbF组Gγ-珠蛋白启动子CC基因型分布明显高于高HbF组。
结论:在进行DNA分析之前,HbE占主导地位且HbF水平低,HbA检测不到的病例可能不如HbE纯合的病例具有定论。在典型的β0-地中海贫血/HbE中,α-地中海贫血的伴随遗传是修饰HbF表达的重要固有因素,和在Gγ-珠蛋白启动子中具有CC基因型的SNP可能表明患有该疾病的患者中HbF表达未升高。