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Krüppel-like factor 1 mutations and expression of hemoglobins F and A2 in homozygous hemoglobin E syndrome

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Abstract

The basis for variability of hemoglobin (Hb) F in homozygous Hb E disease is not well understood. We have examined multiple mutations of the Krüppel-like factor 1 (KLF1) gene; an erythroid specific transcription factor and determined their associations with Hbs F and A2 expression in homozygous Hb E. Four KLF1 mutations including G176AfsX179, T334R, R238H, and −154 (C-T) were screened using specific PCR assays on 461 subjects with homozygous Hb E and 100 normal controls. None of these four mutations were observed in 100 normal controls. Among 461 subjects with homozygous Hb E, 306 had high (≥5 %) and 155 had low (<5 %) Hb F. DNA analysis identified the KLF1 mutations in 35 cases of the former group with high Hb F, including the G176AfsX179 mutation (17/306 = 5.6 %), T334R mutation (9/306 = 2.9 %), −154 (C-T) mutation (7/306 = 2.3 %), and R328H mutation (2/306 = 0.7 %). Only two subjects in the latter group with low Hb F carried the G176AfsX179 and −154 (C-T) mutations. Significant higher Hb A2 level was observed in those of homozygous Hb E with the G176AfsX179 mutation as compared to those without KLF1 mutations. These results indicate that KLF1 is among the genetic factors associated with increased Hbs F and A2, and in combination with other factors could explain the variabilities of these Hb expression in Hb E syndrome.

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Acknowledgments

This work was supported by grants to SF from the National Research University program of Khon Kaen University and the Office of the Higher Education Commission, Ministry of Education, Thailand, and to SY from the Thailand Research Fund (TRG5780067) Thailand. WT is supported by the Royal Golden Jubilee PhD program of the Thailand Research Fund (TRF) (PHD/0305/2552).

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The authors declare that they have no conflict of interest.

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    Authors and Affiliations

    1. Biomedical Science Program, Graduate School, Khon Kaen University, Khon Kaen, 40002, Thailand

      Wanicha Tepakhan

    2. Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, 40002, Thailand

      Wanicha Tepakhan, Supawadee Yamsri, Goonnapa Fucharoen, Kanokwan Sanchaisuriya & Supan Fucharoen

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    1. Wanicha Tepakhan
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    2. Supawadee Yamsri
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    3. Goonnapa Fucharoen
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    4. Kanokwan Sanchaisuriya
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    5. Supan Fucharoen
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    Correspondence to Supan Fucharoen.

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    Wanicha Tepakhan and Supawadee Yamsri contributed equally to this work.

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    Tepakhan, W., Yamsri, S., Fucharoen, G. et al. Krüppel-like factor 1 mutations and expression of hemoglobins F and A2 in homozygous hemoglobin E syndrome. Ann Hematol 94, 1093–1098 (2015). https://doi.org/10.1007/s00277-015-2335-x

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    • DOI: https://doi.org/10.1007/s00277-015-2335-x

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