Skip to main content
SpringerLink
Log in

Association of SNP in exon 1 of HBS1L with hemoglobin F level in β0-thalassemia/hemoglobin E

  • Rapid Communication
  • Published:
International Journal of Hematology Aims and scope Submit manuscript

Abstract

Increase in fetal hemoglobin (Hb F) reduces globin chain imbalance in β-thalassemia, consequently improving symptoms. QTL mapping together with previous genome-wide association study involving approximately 110,000 gene-based SNPs in mild and severe β0-thalassemia/Hb E patients revealed SNPs in HBS1L significantly associated with severity and Hb F levels. Given its potential as binding site for transcription factor activator protein 4, HBS1L exon 1 C32T polymorphism was genotyped in 455 cases, providing for the first time evidence that C allele is associated with elevated Hb F level among β0-thalassemia/Hb E patients with XmnI-Gγ−/−and XmnI-Gγ+/−polymorphisms.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

References

  1. Thein SL. Pathophysiology of β thalassemia—a guide to molecular therapies. Hematology. 2005;2005:31–7.

    Article  Google Scholar 

  2. Fucharoen S, Winichagoon P. Clinical and hematologic aspects of hemoglobin E beta-thalassemia. Curr Opin Hematol. 2000;7:106–12. doi:10.1097/00062752-200003000-00006.

    Article  CAS  PubMed  Google Scholar 

  3. Rees DC, Porter JB, Clegg JB, Weatherall DJ. Why are hemoglobin F levels increased in HbE/beta thalassemia? Blood. 1999;94:3199–204.

    CAS  PubMed  Google Scholar 

  4. Garner C, Tatu T, Reittie JE, Littlewood T, Darley J, Cervino S, et al. Genetic influences on F cells and other hematologic variables: a twin heritability study. Blood. 2000;95:342–6.

    CAS  PubMed  Google Scholar 

  5. Close J, Game L, Clark B, Bergounioux J, Gerovassili A, Thein SL. Genome annotation of a 1.5 Mb region of human chromosome 6q23 encompassing a quantitative trait locus for fetal hemoglobin expression in adults. BMC Genomics. 2004;5:33. doi:10.1186/1471-2164-5-33.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Garner C, Mitchell J, Hatzis T, Reittie J, Farrall M, Thein SL. Haplotype mapping of a major quantitative-trait locus for fetal hemoglobin production, on chromosome 6q23. Am J Hum Genet. 1998;62:1468–74. doi:10.1086/301859.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Craig JE, Rochette J, Fisher CA, Weatherall DJ, Marc S, Lathrop GM, et al. Dissecting the loci controlling fetal haemoglobin production on chromosomes 11p and 6q by the regressive approach. Nat Genet. 1996;12:58–64. doi:10.1038/ng0196-58.

    Article  CAS  PubMed  Google Scholar 

  8. Garner CP, Tatu T, Best S, Creary L, Thein SL. Evidence of genetic interaction between the beta-globin complex and chromosome 8q in the expression of fetal hemoglobin. Am J Hum Genet. 2002;70:793–9. doi:10.1086/339248.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Wyszynski DF, Baldwin CT, Cleves MA, Amirault Y, Nolan VG, Farrell JJ, et al. Polymorphisms near a chromosome 6q QTL area are associated with modulation of fetal hemoglobin levels in sickle cell anemia. Cell Mol Biol Noisy-le-grand. 2004;50:23–33.

    CAS  PubMed  Google Scholar 

  10. Sripichai O, Whitacre J, Munkongdee T, Kumkhaek C, Makarasara W, Winichagoon P, et al. Genetic Analysis of Candidate Modifier Polymorphisms in Hb E-{beta}0-Thalassemia Patients. Ann N Y Acad Sci. 2005;1054:433–8. doi:10.1196/annals.1345.066.

    Article  CAS  PubMed  Google Scholar 

  11. Sripichai O, Makarasara W, Munkongdee T, Kumkhaek C, Nuchprayoon I, Chuansumrit A, et al. A scoring system for the classification of beta-thalassemia/Hb E disease severity. Am J Hematol. 2008;83:482–4. doi:10.1002/ajh.21130.

    Article  PubMed  Google Scholar 

  12. Tsunoda T, Takagi T. Estimating transcription factor bindability on DNA. Bioinformatics. 1999;15:622–30. doi:10.1093/bioinformatics/15.7.622.

    Article  CAS  PubMed  Google Scholar 

  13. Winichagoon P, Fucharoen S, Wilairat P, Chihara K, Fukumaki Y. Nondeletional type of hereditary persistence of fetal haemoglobin: molecular characterization of three unrelated Thai HPFH. Br J Haematol. 1994;87:797–804. doi:10.1111/j.1365-2141.1994.tb06740.x.

    Article  CAS  PubMed  Google Scholar 

  14. Cheng CK, Hoo RLC, Chow BKC, Leung PCK. Functional cooperation between multiple regulatory elements in the untranslated exon 1 stimulates the basal transcription of the human GnRH-II gene. Mol Endocrinol. 2003;17:1175–91. doi:10.1210/me.2002-0418.

    Article  CAS  PubMed  Google Scholar 

  15. Boulanger A, Liu S, Henningsgaard AA, Yu S, Redmond TM. The upstream region of the Rpe65 gene confers retinal pigment epithelium-specific expression in vivo and in vitro and contains critical octamer and e-box binding sites. J Biol Chem. 2000;275:31274–82. doi:10.1074/jbc.M003441200.

    Article  CAS  PubMed  Google Scholar 

  16. Hu YF, Luscher B, Admon A, Mermod N, Tjian R. Transcription factor AP-4 contains multiple dimerization domains that regulate dimer specificity. Genes Dev. 1990;4:1741–52. doi:10.1101/gad.4.10.1741.

    Article  CAS  PubMed  Google Scholar 

  17. Cui Y, Narayanan CS, Zhou J, Kumar A. Exon-I is involved in positive as well as negative regulation of human angiotensinogen gene expression. Gene. 1998;224:97–107. doi:10.1016/S0378-1119(98)00512-5.

    Article  CAS  PubMed  Google Scholar 

  18. Aranburu A, Carlsson R, Persson C, Leanderson T. Transcription factor AP-4 is a ligand for immunoglobulin-kappa promoter E-box elements. Biochem J. 2001;354:431–8. doi:10.1042/0264-6021:3540431.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Wallrapp C, Verrier SB, Zhouravleva G, Philippe H, Philippe M, Gress TM, et al. The product of the mammalian orthologue of the Saccharomyces cerevisiae HBS1 gene is phylogenetically related to eukaryotic release factor 3 (eRF3) but does not carry eRF3-like activity. FEBS Lett. 1998;440:387–92. doi:10.1016/S0014-5793(98)01492-6.

    Article  CAS  PubMed  Google Scholar 

  20. Doma MK, Parker R. Endonucleolytic cleavage of eukaryotic mRNAs with stalls in translation elongation. Nature. 2006;440:561–4. doi:10.1038/nature04530.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This work was supported by National Center for Genetic Engineering and Biotechnology (BIOTEC), Thailand and the Thailand Research Fund. We are grateful to Dr. Prapon Wilairat for proof reading the manuscript.

Author information

Authors and Affiliations

  1. Thalassemia Research Center, Institute of Science and Technology for Research and Development, Mahidol University, Salaya Campus, Nakornpathom, Thailand

    Riyaz A. Pandit, Saovaros Svasti, Orapan Sripichai, Thongperm Munkongdee, Pranee Winichagoon & Suthat Fucharoen

  2. Institute of Molecular Biology and Genetics, Mahidol University, Salaya Campus, Nakornpathom, Thailand

    Riyaz A. Pandit & Kanokporn Triwitayakorn

  3. Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, Thailand

    Saovaros Svasti & Orapan Sripichai

  4. Department of Biochemistry, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand

    Thongperm Munkongdee, Suthat Fucharoen & Chayanon Peerapittayamongkol

Authors
  1. Riyaz A. Pandit
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Saovaros Svasti
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Orapan Sripichai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Thongperm Munkongdee
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kanokporn Triwitayakorn
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Pranee Winichagoon
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Suthat Fucharoen
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Chayanon Peerapittayamongkol
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chayanon Peerapittayamongkol.

About this article

Cite this article

Pandit, R.A., Svasti, S., Sripichai, O. et al. Association of SNP in exon 1 of HBS1L with hemoglobin F level in β0-thalassemia/hemoglobin E. Int J Hematol 88, 357–361 (2008). https://doi.org/10.1007/s12185-008-0167-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12185-008-0167-3

Keywords

Search

Navigation