镰状细胞贫血患者HS2-LCR和Gγ-珠蛋白基因启动子区域的序列变化。
Sequence change in the HS2-LCR and Ggamma-globin gene promoter region of sickle cell anemia patients.
作者信息
Adorno E V, Moura-Neto J P, Lyra I, Zanette A, Santos L F O, Seixas M O, Reis M G, Goncalves M S
机构信息
Laboratório de Patologia e Biologia Molecular, Centro de Pesquisas Gonçalo Moniz, FIOCRUZ, Salvador, BA, Brasil.
出版信息
Braz J Med Biol Res. 2008 Feb;41(2):95-8. doi: 10.1590/s0100-879x2008005000002. Epub 2008 Jan 11.
The fetal hemoglobin (HbF) levels and betaS-globin gene haplotypes of 125 sickle cell anemia patients from Brazil were investigated. We sequenced the Ggamma- and Agamma-globin gene promoters and the DNase I-2 hypersensitive sites in the locus control regions (HS2-LCR) of patients with HbF level disparities as compared to their betaS haplotypes. Sixty-four (51.2%) patients had CAR/Ben genotype; 36 (28.8%) Ben/Ben; 18 (14.4%) CAR/CAR; 2 (1.6%) CAR/Atypical; 2 (1.6%) Ben/Cam; 1 (0.8%) CAR/Cam; 1 (0.8%) CAR/Arab-Indian, and 1 (0.8%) Sen/Atypical. The HS2-LCR sequence analyses demonstrated a c.-10.677G>A change in patients with the Ben haplotype and high HbF levels. The Gg gene promoter sequence analyses showed a c.-157T>C substitution shared by all patients, and a c.-222_-225del related to the Cam haplotype. These results identify new polymorphisms in the HS2-LCR and Gg-globin gene promoter. Further studies are required to determine the correlation between HbF synthesis and the clinical profile of sickle cell anemia patients.
对来自巴西的125例镰状细胞贫血患者的胎儿血红蛋白（HbF）水平和βS-珠蛋白基因单倍型进行了研究。我们对HbF水平与其βS单倍型存在差异的患者的Gγ-和Aγ-珠蛋白基因启动子以及基因座控制区（HS2-LCR）中的DNase I-2高敏位点进行了测序。64例（51.2%）患者为CAR/Ben基因型；36例（28.8%）为Ben/Ben；18例（14.4%）为CAR/CAR；2例（1.6%）为CAR/非典型；2例（1.6%）为Ben/Cam；1例（0.8%）为CAR/Cam；1例（0.8%）为CAR/阿拉伯-印度型，以及1例（0.8%）为Sen/非典型。HS2-LCR序列分析显示具有Ben单倍型且HbF水平高的患者存在c.-10.677G>A变化。Gg基因启动子序列分析显示所有患者均存在c.-157T>C替换，以及与Cam单倍型相关的c.-222_-225缺失。这些结果确定了HS2-LCR和Gg-珠蛋白基因启动子中的新多态性。需要进一步研究以确定HbF合成与镰状细胞贫血患者临床特征之间的相关性。
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