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

doi:10.1038/sj.tpj.6500433

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

Pulmonary Disease

Research output: Contribution to journal › Article › peer-review

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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 language	English (US)
Pages (from-to)	386-394
Number of pages	9
Journal	Pharmacogenomics Journal
Volume	7
Issue number	6
DOIs	https://doi.org/10.1038/sj.tpj.6500433
State	Published - Dec 2007

ASJC Scopus subject areas

Molecular Medicine
Genetics
Pharmacology

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@article{ffa1bcf2c8f64917b56e6594cba148d1,

title = "Fetal hemoglobin in sickle cell anemia: Genetic determinants of response to hydroxyurea",

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.",

author = "Q. Ma and Wyszynski, {D. F.} and Farrell, {J. J.} and Abdullah Kutlar and Farrer, {L. A.} and Baldwin, {C. T.} and Steinberg, {M. H.}",

note = "Funding Information: We thank the investigators of the MSH who obtained blood samples for DNA-based studies and analyzed data from these studies for the study publications cited in the text of this paper. This study was supported by NHLBI Grant HL R01 70735 (MHS).",

year = "2007",

month = dec,

doi = "10.1038/sj.tpj.6500433",

language = "English (US)",

volume = "7",

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AU - Ma, Q.

AU - Wyszynski, D. F.

AU - Farrell, J. J.

AU - Kutlar, Abdullah

AU - Farrer, L. A.

AU - Baldwin, C. T.

AU - Steinberg, M. H.

N1 - Funding Information: We thank the investigators of the MSH who obtained blood samples for DNA-based studies and analyzed data from these studies for the study publications cited in the text of this paper. This study was supported by NHLBI Grant HL R01 70735 (MHS).

PY - 2007/12

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N2 - 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.

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