Open AccessAssociation of polymorphisms in the HBG1‐HBD intergenic region with HbF levels
Author(s) -
Hu Li,
Huang Ling,
Han Yuanyuan,
Jin Tingting,
Liu Juan,
Jiang Minmin,
Liu Xingmei,
Li Yuanyuan,
Han Wenping,
An Bangquan,
Huang Shengwen
Publication year - 2020
Publication title -
journal of clinical laboratory analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.536
H-Index - 50
eISSN - 1098-2825
pISSN - 0887-8013
DOI - 10.1002/jcla.23243
Subject(s) - haplotype , intergenic region , single nucleotide polymorphism , genetics , fetal hemoglobin , genotype , biology , snp , sanger sequencing , microbiology and biotechnology , gene , mutation , genome , fetus , pregnancy
Background 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. Methods 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. Results 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. Conclusion 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.