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

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Abstract

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.

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Acknowledgments

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).

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Authors and Affiliations

  1. Department of Pathology, Maha Chakri Sirindhorn Medical Center, Faculty of Medicine, Srinakharinwirot University, Nakhon Nayok, Thailand

    Wittaya Jomoui

  2. Department of Pathology, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand

    Wanicha Tepakhan

  3. Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand

    Supawadee Yamsri, Hataichanok Srivorakun, Goonnapa Fucharoen & Supan Fucharoen

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  1. Wittaya Jomoui
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  2. Wanicha Tepakhan
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  3. Supawadee Yamsri
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  4. Hataichanok Srivorakun
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  5. Goonnapa Fucharoen
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  6. Supan Fucharoen
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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.

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Correspondence to Wittaya Jomoui.

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Jomoui, W., Tepakhan, W., Yamsri, S. et al. A novel SNP rs11759328 on Rho GTPase-activating protein 18 gene is associated with the expression of Hb F in hemoglobin E-related disorders. Ann Hematol 99, 23–29 (2020). https://doi.org/10.1007/s00277-019-03862-0

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  • DOI: https://doi.org/10.1007/s00277-019-03862-0

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