A novel SNP rs11759328 on Rho GTPase-activating protein 18 gene is associated with the expression of Hb F in hemoglobin E-related disorders

  • Wittaya JomouiEmail author
  • Wanicha Tepakhan
  • Supawadee Yamsri
  • Hataichanok Srivorakun
  • Goonnapa Fucharoen
  • Supan Fucharoen
Original Article


Hemoglobin (Hb) F has a modulatory effect on the clinical phenotype of β-thalassemia disease. High expression of Hb F in Hb E-related disorders has been noted, but the mechanism is not well understood. We have examined the association of a novel SNP rs11759328 on ARHGAP 18 gene and other known modulators with a variability of Hb F in Hb E-related disorders. Genotyping of SNP rs11759328 (G/A) was performed based on high-resolution melting analysis. The rs11759328 (A allele) was shown to be significantly associated with Hb F levels (p < 0.05) in heterozygous and homozygous Hb E. High levels of Hb F in both heterozygous and homozygous Hb E were also found to be associated with SNPs in the study of other modifying genes including KLF 1 mutation, rs7482144 (Gγ-XmnI), rs4895441, rs9399137 of (HBS1L-MYB), and rs4671393 (BCL11A). Multivariate analysis showed that KLF1 mutation and SNP rs11759328 (GA) (ARHGAP18) modulated Hb F expression in heterozygous Hb E. For homozygous Hb E, this was found to be related to five modifying factors, i.e., KLF1 mutation, rs4895441 (GG), rs9399137 (CC), rs4671393 (AA), and rs4671393 (GA). These results indicate that a novel SNP rs11759328 is a genetically modifying factor associated with increased Hb F in Hb E disorder.


ARHGAP 18 gene Hemoglobin E Hemoglobin F SNP rs11759328 



The researchers thank Mr. Robert Areelon, who is a native speaker for helpful comments and proofread on the manuscript. WJ is supported by the Royal Golden Jubilee PhD Advanced program (Contract no. RAP61K0018) of the Thailand Research Fund. SF is a recipient of the TRF Research Team Promotion Grant (RTA) of the Thailand Science Research and Innovation (TSRI), Thailand (Contract ID RTA6280005).

Authors’ contributions

WJ performed the experiment and wrote the initial manuscript. GF helped in research design and data analysis. HS, WT, and SY helped in data analysis and provided suggestions. WJ and SF were involved in research design, analysis of data, and acquisition of the grant, editing, and guaranteeing the paper. All authors approved the final version.

Compliance with ethical standards

Conflict of interests

The authors declare that they have no conflict of interest.

Supplementary material

277_2019_3862_MOESM1_ESM.pdf (507 kb)
ESM 1 (PDF 507 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Wittaya Jomoui
    • 1
    Email author
  • Wanicha Tepakhan
    • 2
  • Supawadee Yamsri
    • 3
  • Hataichanok Srivorakun
    • 3
  • Goonnapa Fucharoen
    • 3
  • Supan Fucharoen
    • 3
  1. 1.Department of Pathology, Maha Chakri Sirindhorn Medical Center, Faculty of MedicineSrinakharinwirot UniversityNakhon NayokThailand
  2. 2.Department of Pathology, Faculty of MedicinePrince of Songkla UniversitySongkhlaThailand
  3. 3.Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical SciencesKhon Kaen UniversityKhon KaenThailand

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