Abstract：
BACKGROUND: Excessive expression of hemoglobin F (HbF) is a characteristic feature and important diagnostic marker of β0-thalassemia/HbE disease. However, some patients may exhibit low-HbF levels, leading to misdiagnosis and precluding genetic counseling. The genetic factors influencing these differences in HbF expression in this atypical disease are not completely understood.
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.
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.
摘要：
背景：血红蛋白F（HbF）的过度表达是β0-地中海贫血/HbE疾病的特征性特征和重要诊断标志物。然而,一些患者可能表现出低HbF水平，导致误诊和排除遗传咨询。影响这种非典型疾病中HbF表达的这些差异的遗传因素尚未完全了解。
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。
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。
