School of Medicine, Guizhou University, Guiyang, China.
Prenatal Diagnosis Center, Guizhou Provincial People's Hospital, Guiyang, China.
J Clin Lab Anal. 2020 Jun;34(6):e23243. doi: 10.1002/jcla.23243. Epub 2020 Feb 18.
Increased levels of fetal hemoglobin (HbF) can improve the clinical course of the patients with sickle cell anemia (SCA) or β-thalassemia. The HBG1-HBD intergenic region plays an important role in this process. However, very few studies investigated whether the variations in this region have an effect on HbF expression.
We retrieved all the SNP data in the HBG1-HBD intergenic region and defined the haplotype blocks, then performed cluster analysis and selected a tagSNP. A total of 500 normal individuals and 300 β-thalassemia carriers were enrolled. After routine blood and hemoglobin capillary electrophoresis testing, β-thalassemia mutations were detected using PCR-reverse dot blot. The genotypes of the rs4910736 (A > C) and rs10128556 (C > T) were determined using Sanger sequencing; the relationship between the two SNPs and the levels of HbF was analyzed.
Two haplotype blocks were constructed. Block 1 included seven haplotypes divided into two groups M and N by 11 tagSNPs, among which rs4910736 was selected as a tagSNP, while block 2 included three haplotypes. We found that the haplotypes of block 1 were statistically associated with HbF levels, but the non-tagSNP rs10128556 was shown to be more strongly associated with HbF levels than rs4910736.
This work proved that the haplotypes in the HBG1-HBD intergenic region and SNP rs10128556 are both statistically associated with HbF levels, revealing the association of polymorphisms in the HBG1-HBD intergenic region with HbF levels.
胎儿血红蛋白（HbF）水平升高可改善镰状细胞贫血（SCA）或β-地中海贫血患者的临床病程。HBG1-HBD 基因间区在这一过程中起着重要作用。然而，很少有研究调查该区域的变异是否对 HbF 表达有影响。
我们检索了 HBG1-HBD 基因间区的所有 SNP 数据，并定义了单倍型块，然后进行聚类分析并选择了一个标签 SNP。共纳入 500 名正常个体和 300 名β-地中海贫血携带者。常规进行血常规和血红蛋白毛细管电泳检测后，采用 PCR-反向斑点杂交检测β-地中海贫血突变。采用 Sanger 测序法检测 rs4910736（A>C）和 rs10128556（C>T）的基因型；分析这两个 SNP 与 HbF 水平的关系。
构建了两个单倍型块。块 1 包括七个单倍型，通过 11 个标签 SNP 分为 M 和 N 两组，其中 rs4910736 被选为标签 SNP，而块 2 包括三个单倍型。我们发现块 1 的单倍型与 HbF 水平有统计学关联，但非标签 SNP rs10128556 与 HbF 水平的关联比 rs4910736 更强。
本研究证明 HBG1-HBD 基因间区的单倍型和 SNP rs10128556 均与 HbF 水平有统计学关联，揭示了 HBG1-HBD 基因间区多态性与 HbF 水平的关联。
