Fetal hemoglobin in sickle cell anemia

Genetic determinants of response to hydroxyurea

Q. Ma, D. F. Wyszynski, J. J. Farrell, Abdullah Kutlar, L. A. Farrer, C. T. Baldwin, M. H. Steinberg

Research output: Contribution to journalArticle

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Abstract

The increase in fetal hemoglobin (HbF) in response to hydroxyurea (HU) varies among patients with sickle cell anemia. Twenty-nine candidate genes within loci previously reported to be linked to HbF level (6q22.3-q23.2, 8q11-q12 and Xp22.2-p22.3), involved in metabolism of HU and related to erythroid progenitor proliferation were studied in 137 sickle cell anemia patients treated with HU. Three-hundred and twenty tagging single nucleotide polymorphisms (SNPs) for genotyping were selected based on HapMap data. Multiple linear regression and the nonlinear regression Random Forest method were used to investigate the association between SNPs and the change in HbF level after 2 years of treatment with HU. Both methods revealed that SNPs in genes within the 6q22.3-23.2 and 8q11-q12 linkage peaks, and also the ARG2, FLT1, HAO2 and NOS1 genes were associated with the HbF response to HU. Polymorphisms in genes regulating HbF expression, HU metabolism and erythroid progenitor proliferation might modulate the patient response to HU.

Original languageEnglish (US)
Pages (from-to)386-394
Number of pages9
JournalPharmacogenomics Journal
Volume7
Issue number6
DOIs
StatePublished - Dec 1 2007

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Fetal Hemoglobin
Hydroxyurea
Sickle Cell Anemia
Single Nucleotide Polymorphism
Genes
HapMap Project
Linear Models

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmacology

Cite this

Ma, Q., Wyszynski, D. F., Farrell, J. J., Kutlar, A., Farrer, L. A., Baldwin, C. T., & Steinberg, M. H. (2007). Fetal hemoglobin in sickle cell anemia: Genetic determinants of response to hydroxyurea. Pharmacogenomics Journal, 7(6), 386-394. https://doi.org/10.1038/sj.tpj.6500433

Fetal hemoglobin in sickle cell anemia : Genetic determinants of response to hydroxyurea. / Ma, Q.; Wyszynski, D. F.; Farrell, J. J.; Kutlar, Abdullah; Farrer, L. A.; Baldwin, C. T.; Steinberg, M. H.

In: Pharmacogenomics Journal, Vol. 7, No. 6, 01.12.2007, p. 386-394.

Research output: Contribution to journalArticle

Ma, Q, Wyszynski, DF, Farrell, JJ, Kutlar, A, Farrer, LA, Baldwin, CT & Steinberg, MH 2007, 'Fetal hemoglobin in sickle cell anemia: Genetic determinants of response to hydroxyurea', Pharmacogenomics Journal, vol. 7, no. 6, pp. 386-394. https://doi.org/10.1038/sj.tpj.6500433
Ma, Q. ; Wyszynski, D. F. ; Farrell, J. J. ; Kutlar, Abdullah ; Farrer, L. A. ; Baldwin, C. T. ; Steinberg, M. H. / Fetal hemoglobin in sickle cell anemia : Genetic determinants of response to hydroxyurea. In: Pharmacogenomics Journal. 2007 ; Vol. 7, No. 6. pp. 386-394.
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