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 | |
| State | Published - Dec 1 2007 |
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ASJC Scopus subject areas
- Molecular Medicine
- Genetics
- Pharmacology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Fetal hemoglobin in sickle cell anemia
T2 - Genetic determinants of response to hydroxyurea
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.
PY - 2007/12/1
Y1 - 2007/12/1
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.
AB - 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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UR - http://www.scopus.com/inward/citedby.url?scp=36549089997&partnerID=8YFLogxK
U2 - 10.1038/sj.tpj.6500433
DO - 10.1038/sj.tpj.6500433
M3 - Article
C2 - 17299377
AN - SCOPUS:36549089997
VL - 7
SP - 386
EP - 394
JO - Pharmacogenomics Journal
JF - Pharmacogenomics Journal
SN - 1470-269X
IS - 6
ER -