Genetic Variants at BCL11A and HBS1L-MYB loci Influence Hb F Levels in Chinese Zhuang β-Thalassemia Intermedia Patients

Hemoglobin. 2016 Nov;40(6):405-410. doi: 10.1080/03630269.2016.1253586.

Abstract

Increased Hb F levels can ameliorate the symptoms of β-thalassemia (β-thal). Due to the genetic heterogenicity of β-thal, the relationship between genetic variants in modifier genes and Hb F level has been studied in different populations. The Chinese Zhuang has the second largest population in China and has 6.78% prevalence of β-thal. However, the effects of these single nucleotide polymorphism (SNP) variants on the Hb F levels of β-thal intermedia (β-TI) patients in this population have not been reported. To explore the association between modifier loci (β-globin gene cluster, HBS1L-MYB intergenic region and BCL11A) and Hb F levels in Chinese Zhuang β-TI patients, 96 unrelated β-TI patients (50 males and 46 females) with different Hb F levels were recruited and genotyped by mass spectrometry. A total of 13 SNPs were confirmed to be in a significant relationship with Hb F levels in this population. Of these, high-risk genotypes of six Hb F-associated SNPs, rs9376090, rs7776054, rs9399137, rs9389268, rs9402685 in the HBS1L-MYB intergenic region and rs189984760 in the BCL11A locus, showed association with high Hb F levels, especially for SNPs in linkage disequilibrium. One novel Hb F-associated SNP, rs189984760, was identified in our study. Our findings will be of valuable reference for correlation between modifier genes and Hb F in Chinese Zhuang populations and may lead to better understand the modifying mechanisms for β-thal.

Keywords: Hb F; genetic variants; modifier loci; single nucleotide polymorphism (SNP); β-Thalassemia intermedia (β-TI).

MeSH terms

  • Adolescent
  • Adult
  • Asian People
  • Carrier Proteins / genetics*
  • Child
  • Child, Preschool
  • DNA, Intergenic
  • Female
  • Fetal Hemoglobin / analysis*
  • GTP-Binding Proteins / genetics*
  • Genes, Modifier
  • Genetic Variation*
  • HSP70 Heat-Shock Proteins / genetics*
  • Humans
  • Male
  • Nuclear Proteins / genetics*
  • Peptide Elongation Factors / genetics*
  • Proto-Oncogene Proteins c-myb / genetics*
  • Repressor Proteins
  • Young Adult
  • beta-Thalassemia / genetics*

Substances

  • BCL11A protein, human
  • Carrier Proteins
  • DNA, Intergenic
  • HSP70 Heat-Shock Proteins
  • Nuclear Proteins
  • Peptide Elongation Factors
  • Proto-Oncogene Proteins c-myb
  • Repressor Proteins
  • Fetal Hemoglobin
  • GTP-Binding Proteins
  • HBS1L protein, human