Fetal hemoglobin in sickle cell anemia: genetic determinants of response to hydroxyurea
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...
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| description | 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. |
| doi_str_mv | 10.1038/sj.tpj.6500433 |
| format | Article |
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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.</description><identifier>ISSN: 1470-269X</identifier><identifier>EISSN: 1473-1150</identifier><identifier>DOI: 10.1038/sj.tpj.6500433</identifier><identifier>PMID: 17299377</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Alcohol Oxidoreductases - genetics ; Anemia ; Anemia, Sickle Cell - blood ; Anemia, Sickle Cell - drug therapy ; Anemia, Sickle Cell - genetics ; Antisickling Agents - metabolism ; Antisickling Agents - therapeutic use ; Arginase - genetics ; Biomedical and Life Sciences ; Biomedicine ; Biotransformation - genetics ; Chromosome 6 ; Chromosomes, Human, Pair 6 ; Chromosomes, Human, Pair 8 ; Double-Blind Method ; Erythropoiesis - genetics ; Fetal Hemoglobin - metabolism ; Fetuses ; Gene Expression ; Genotype ; Genotyping ; Hemoglobin ; Human Genetics ; Humans ; Hydroxyurea ; Hydroxyurea - metabolism ; Hydroxyurea - therapeutic use ; Linkage Disequilibrium ; Metabolism ; Nitric Oxide Synthase Type I - genetics ; Nitric-oxide synthase ; Oncology ; original-article ; Patients ; Pharmacotherapy ; Phenotype ; Polymorphism, Single Nucleotide ; Psychopharmacology ; Severity of Illness Index ; Sickle cell anemia ; Sickle cell disease ; Single-nucleotide polymorphism ; Time Factors ; Treatment Outcome ; United States ; Vascular Endothelial Growth Factor Receptor-1 - genetics</subject><ispartof>The pharmacogenomics journal, 2007-12, Vol.7 (6), p.386-394</ispartof><rights>Springer Nature Limited 2007</rights><rights>COPYRIGHT 2007 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Dec 2007</rights><rights>Nature Publishing Group 2007.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c458t-d2f422ae393e6d83757cc8663b32d06b55d1d0bf15250f3ca6c6d350e4cfcfcd3</citedby><cites>FETCH-LOGICAL-c458t-d2f422ae393e6d83757cc8663b32d06b55d1d0bf15250f3ca6c6d350e4cfcfcd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17299377$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ma, Q</creatorcontrib><creatorcontrib>Wyszynski, D F</creatorcontrib><creatorcontrib>Farrell, J J</creatorcontrib><creatorcontrib>Kutlar, A</creatorcontrib><creatorcontrib>Farrer, L A</creatorcontrib><creatorcontrib>Baldwin, C T</creatorcontrib><creatorcontrib>Steinberg, M H</creatorcontrib><title>Fetal hemoglobin in sickle cell anemia: genetic determinants of response to hydroxyurea</title><title>The pharmacogenomics journal</title><addtitle>Pharmacogenomics J</addtitle><addtitle>Pharmacogenomics J</addtitle><description>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.</description><subject>Alcohol Oxidoreductases - genetics</subject><subject>Anemia</subject><subject>Anemia, Sickle Cell - blood</subject><subject>Anemia, Sickle Cell - drug therapy</subject><subject>Anemia, Sickle Cell - genetics</subject><subject>Antisickling Agents - metabolism</subject><subject>Antisickling Agents - therapeutic use</subject><subject>Arginase - genetics</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Biotransformation - genetics</subject><subject>Chromosome 6</subject><subject>Chromosomes, Human, Pair 6</subject><subject>Chromosomes, Human, Pair 8</subject><subject>Double-Blind Method</subject><subject>Erythropoiesis - genetics</subject><subject>Fetal Hemoglobin - metabolism</subject><subject>Fetuses</subject><subject>Gene Expression</subject><subject>Genotype</subject><subject>Genotyping</subject><subject>Hemoglobin</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Hydroxyurea</subject><subject>Hydroxyurea - metabolism</subject><subject>Hydroxyurea - therapeutic use</subject><subject>Linkage Disequilibrium</subject><subject>Metabolism</subject><subject>Nitric Oxide Synthase Type I - genetics</subject><subject>Nitric-oxide synthase</subject><subject>Oncology</subject><subject>original-article</subject><subject>Patients</subject><subject>Pharmacotherapy</subject><subject>Phenotype</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Psychopharmacology</subject><subject>Severity of Illness Index</subject><subject>Sickle cell anemia</subject><subject>Sickle cell disease</subject><subject>Single-nucleotide polymorphism</subject><subject>Time Factors</subject><subject>Treatment Outcome</subject><subject>United States</subject><subject>Vascular Endothelial Growth Factor Receptor-1 - genetics</subject><issn>1470-269X</issn><issn>1473-1150</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqFkUFr3DAQhU1paNK01x6LaKE3b0aSJdu9hdAkhUAuLe1NyNJ4I9eWtpIN2X8fbXdhoRDCCCSkbx5P84riA4UVBd5cpGE1b4aVFAAV56-KM1rVvKRUwOt_ZyiZbH-fFm9TGgCopHXzpjilNWtbXtdnxa9rnPVIHnAK6zF0zpO8kjN_RiQGx5Foj5PTX8kaPc7OEIszxsl57edEQk8ipk3wCckcyMPWxvC4XSLqd8VJr8eE7w_7efHz-tuPq9vy7v7m-9XlXWkq0cylZX3FmEbecpS24bWojWmk5B1nFmQnhKUWup4KJqDnRksjLReAlelzWX5efNnrbmL4u2Ca1eTSznj2HZakZCOqNqu-CLI8TQkgMvj5P3AIS_T5E4rJisq2AZCZ-vQsxRqQmWwztNpDaz2icr4Pc9Qml80zNcFj7_L9JW2B7qLhxwYTQ0oRe7WJbtJxqyioXd4qDSrnrQ5554aPBxtLN6E94oeAM3CxB1J-8muMR5_PSD4B9vO2BQ</recordid><startdate>20071201</startdate><enddate>20071201</enddate><creator>Ma, Q</creator><creator>Wyszynski, D F</creator><creator>Farrell, J J</creator><creator>Kutlar, A</creator><creator>Farrer, L A</creator><creator>Baldwin, C T</creator><creator>Steinberg, M H</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QP</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20071201</creationdate><title>Fetal hemoglobin in sickle cell anemia: genetic determinants of response to hydroxyurea</title><author>Ma, Q ; Wyszynski, D F ; Farrell, J J ; Kutlar, A ; Farrer, L A ; Baldwin, C T ; Steinberg, M H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c458t-d2f422ae393e6d83757cc8663b32d06b55d1d0bf15250f3ca6c6d350e4cfcfcd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Alcohol Oxidoreductases - genetics</topic><topic>Anemia</topic><topic>Anemia, Sickle Cell - blood</topic><topic>Anemia, Sickle Cell - drug therapy</topic><topic>Anemia, Sickle Cell - genetics</topic><topic>Antisickling Agents - metabolism</topic><topic>Antisickling Agents - therapeutic use</topic><topic>Arginase - genetics</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Biotransformation - genetics</topic><topic>Chromosome 6</topic><topic>Chromosomes, Human, Pair 6</topic><topic>Chromosomes, Human, Pair 8</topic><topic>Double-Blind Method</topic><topic>Erythropoiesis - genetics</topic><topic>Fetal Hemoglobin - metabolism</topic><topic>Fetuses</topic><topic>Gene Expression</topic><topic>Genotype</topic><topic>Genotyping</topic><topic>Hemoglobin</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Hydroxyurea</topic><topic>Hydroxyurea - metabolism</topic><topic>Hydroxyurea - therapeutic use</topic><topic>Linkage Disequilibrium</topic><topic>Metabolism</topic><topic>Nitric Oxide Synthase Type I - genetics</topic><topic>Nitric-oxide synthase</topic><topic>Oncology</topic><topic>original-article</topic><topic>Patients</topic><topic>Pharmacotherapy</topic><topic>Phenotype</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Psychopharmacology</topic><topic>Severity of Illness Index</topic><topic>Sickle cell anemia</topic><topic>Sickle cell disease</topic><topic>Single-nucleotide polymorphism</topic><topic>Time Factors</topic><topic>Treatment Outcome</topic><topic>United States</topic><topic>Vascular Endothelial Growth Factor Receptor-1 - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ma, Q</creatorcontrib><creatorcontrib>Wyszynski, D F</creatorcontrib><creatorcontrib>Farrell, J J</creatorcontrib><creatorcontrib>Kutlar, A</creatorcontrib><creatorcontrib>Farrer, L A</creatorcontrib><creatorcontrib>Baldwin, C T</creatorcontrib><creatorcontrib>Steinberg, M H</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The pharmacogenomics journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ma, Q</au><au>Wyszynski, D F</au><au>Farrell, J J</au><au>Kutlar, A</au><au>Farrer, L A</au><au>Baldwin, C T</au><au>Steinberg, M H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Fetal hemoglobin in sickle cell anemia: genetic determinants of response to hydroxyurea</atitle><jtitle>The pharmacogenomics journal</jtitle><stitle>Pharmacogenomics J</stitle><addtitle>Pharmacogenomics J</addtitle><date>2007-12-01</date><risdate>2007</risdate><volume>7</volume><issue>6</issue><spage>386</spage><epage>394</epage><pages>386-394</pages><issn>1470-269X</issn><eissn>1473-1150</eissn><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.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>17299377</pmid><doi>10.1038/sj.tpj.6500433</doi><tpages>9</tpages></addata></record> |
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| ispartof | The pharmacogenomics journal, 2007-12, Vol.7 (6), p.386-394 |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Alcohol Oxidoreductases - genetics Anemia Anemia, Sickle Cell - blood Anemia, Sickle Cell - drug therapy Anemia, Sickle Cell - genetics Antisickling Agents - metabolism Antisickling Agents - therapeutic use Arginase - genetics Biomedical and Life Sciences Biomedicine Biotransformation - genetics Chromosome 6 Chromosomes, Human, Pair 6 Chromosomes, Human, Pair 8 Double-Blind Method Erythropoiesis - genetics Fetal Hemoglobin - metabolism Fetuses Gene Expression Genotype Genotyping Hemoglobin Human Genetics Humans Hydroxyurea Hydroxyurea - metabolism Hydroxyurea - therapeutic use Linkage Disequilibrium Metabolism Nitric Oxide Synthase Type I - genetics Nitric-oxide synthase Oncology original-article Patients Pharmacotherapy Phenotype Polymorphism, Single Nucleotide Psychopharmacology Severity of Illness Index Sickle cell anemia Sickle cell disease Single-nucleotide polymorphism Time Factors Treatment Outcome United States Vascular Endothelial Growth Factor Receptor-1 - genetics |
| title | Fetal hemoglobin in sickle cell anemia: genetic determinants of response to hydroxyurea |
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