Association between Different Polymorphic Markers and β-Thalassemia Intermedia in Central Iran

Hemoglobin. 2020 Jan;44(1):27-30. doi: 10.1080/03630269.2019.1709204. Epub 2020 Jan 3.


β-Thalassemia intermedia (β-TI) is a clinical condition characterized by moderate, non transfusional anemia and hepatosplenomegaly. The main objective of this study was to determine the molecular basis of the clinical phenotype of β-TI in Iran. To elucidate the mild phenotype of many patients with β-TI, we screened for three prevalent β-globin gene mutations [IVS-II-1 (G>A) HBB: c.315+1G>A, IVS-I-110 (G>A) HBB: c.93-21G>A and IVS-I-5 (G>C) [HBB: c.92+5G>C], deletions on the α-globin genes, XmnI polymorphisms and restriction fragment length polymorphism (RFLP) haplotypes on the β-globin gene cluster in 50 β-TI patients. Fifty-eight percent of the patients (29 cases) were associated with the mentioned mutations. We showed that the HBB: c.315+1G>A mutation is linked to haplotype [+ - + +] (57.69%). This haplotype is in linkage disequilibrium with the XmnI polymorphism (NG_000007.3: g.42677C>T) and has been associated with increased expression of Hb F in β-TI patients. The XmnI polymorphism is defined in association with this prevalent mutation. Two patients had a single α-globin gene deletion [-α3.7 (rightward) deletion]. The main genetic factor in mild phenotype β-TI patients is the linkage of an XmnI polymorphism (NG_000007.3: g.42677C>T) with the HBB: c.315+1G>A (80.76%), which is associated with increased production of Hb F and coinheritance of haplotype [+ - + +] with β-TI, especially with the homozygous HBB: c.315+1G>A mutation. Molecular basis of β-TI could be explained by the involvement of different factors that tend to develop the disease phenotype.

Keywords: HBB: c.315+1G>A; HBB: c.92+5G>C; HBB: c.93-21G>A; Xmnl polymorphism; haplotype; β-Thalassemia intermedia (β-TI).

MeSH terms

  • Adult
  • Anemia, Hypochromic / diagnosis
  • Anemia, Hypochromic / genetics*
  • Anemia, Hypochromic / pathology
  • Female
  • Fetal Hemoglobin / genetics*
  • Gene Expression
  • Haplotypes
  • Hemoglobins, Abnormal / genetics*
  • Hepatomegaly / diagnosis
  • Hepatomegaly / genetics
  • Hepatomegaly / pathology
  • Humans
  • Iran
  • Linkage Disequilibrium
  • Male
  • Mutation*
  • Phenotype
  • Polymorphism, Restriction Fragment Length
  • Sequence Analysis, DNA
  • Splenomegaly / diagnosis
  • Splenomegaly / genetics
  • Splenomegaly / pathology
  • alpha-Globins / deficiency
  • alpha-Globins / genetics*
  • beta-Globins / deficiency
  • beta-Globins / genetics*
  • beta-Thalassemia / diagnosis
  • beta-Thalassemia / genetics*
  • beta-Thalassemia / pathology


  • Hemoglobins, Abnormal
  • alpha-Globins
  • beta-Globins
  • Fetal Hemoglobin