DNA polymorphisms at the BCL11A, HBS1L-MYB, and beta-globin loci associate with fetal hemoglobin levels and pain crises in sickle cell disease
Sickle cell disease (SCD) is a debilitating monogenic blood disorder with a highly variable phenotype characterized by severe pain crises, acute clinical events, and early mortality. Interindividual variation in fetal hemoglobin (HbF) expression is a known and potentially heritable modifier of SCD s...
Saved in:
| Published in: | Proceedings of the National Academy of Sciences - PNAS Vol. 105; no. 33; p. 11869 |
|---|---|
| Main Authors: | , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
United States
19.08.2008
|
| Subjects: | |
| ISSN: | 1091-6490, 1091-6490 |
| Online Access: | Get more information |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Abstract | Sickle cell disease (SCD) is a debilitating monogenic blood disorder with a highly variable phenotype characterized by severe pain crises, acute clinical events, and early mortality. Interindividual variation in fetal hemoglobin (HbF) expression is a known and potentially heritable modifier of SCD severity. High HbF levels are correlated with reduced morbidity and mortality. Common single nucleotide polymorphisms (SNPs) at the BCL11A and HBS1L-MYB loci have been implicated previously in HbF level variation in nonanemic European populations. We recently demonstrated an association between a BCL11A SNP and HbF levels in one SCD cohort [Uda M, et al. (2008) Proc Natl Acad Sci USA 105:1620-1625]. Here, we genotyped additional BCL11A SNPs, HBS1L-MYB SNPs, and an SNP upstream of (G)gamma-globin (HBG2; the XmnI polymorphism), in two independent SCD cohorts: the African American Cooperative Study of Sickle Cell Disease (CSSCD) and an SCD cohort from Brazil. We studied the effect of these SNPs on HbF levels and on a measure of SCD-related morbidity (pain crisis rate). We strongly replicated the association between these SNPs and HbF level variation (in the CSSCD, P values range from 0.04 to 2 x 10(-42)). Together, common SNPs at the BCL11A, HBS1L-MYB, and beta-globin (HBB) loci account for >20% of the variation in HbF levels in SCD patients. We also have shown that HbF-associated SNPs associate with pain crisis rate in SCD patients. These results provide a clear example of inherited common sequence variants modifying the severity of a monogenic disease. |
|---|---|
| AbstractList | Sickle cell disease (SCD) is a debilitating monogenic blood disorder with a highly variable phenotype characterized by severe pain crises, acute clinical events, and early mortality. Interindividual variation in fetal hemoglobin (HbF) expression is a known and potentially heritable modifier of SCD severity. High HbF levels are correlated with reduced morbidity and mortality. Common single nucleotide polymorphisms (SNPs) at the BCL11A and HBS1L-MYB loci have been implicated previously in HbF level variation in nonanemic European populations. We recently demonstrated an association between a BCL11A SNP and HbF levels in one SCD cohort [Uda M, et al. (2008) Proc Natl Acad Sci USA 105:1620-1625]. Here, we genotyped additional BCL11A SNPs, HBS1L-MYB SNPs, and an SNP upstream of (G)gamma-globin (HBG2; the XmnI polymorphism), in two independent SCD cohorts: the African American Cooperative Study of Sickle Cell Disease (CSSCD) and an SCD cohort from Brazil. We studied the effect of these SNPs on HbF levels and on a measure of SCD-related morbidity (pain crisis rate). We strongly replicated the association between these SNPs and HbF level variation (in the CSSCD, P values range from 0.04 to 2 x 10(-42)). Together, common SNPs at the BCL11A, HBS1L-MYB, and beta-globin (HBB) loci account for >20% of the variation in HbF levels in SCD patients. We also have shown that HbF-associated SNPs associate with pain crisis rate in SCD patients. These results provide a clear example of inherited common sequence variants modifying the severity of a monogenic disease. Sickle cell disease (SCD) is a debilitating monogenic blood disorder with a highly variable phenotype characterized by severe pain crises, acute clinical events, and early mortality. Interindividual variation in fetal hemoglobin (HbF) expression is a known and potentially heritable modifier of SCD severity. High HbF levels are correlated with reduced morbidity and mortality. Common single nucleotide polymorphisms (SNPs) at the BCL11A and HBS1L-MYB loci have been implicated previously in HbF level variation in nonanemic European populations. We recently demonstrated an association between a BCL11A SNP and HbF levels in one SCD cohort [Uda M, et al. (2008) Proc Natl Acad Sci USA 105:1620-1625]. Here, we genotyped additional BCL11A SNPs, HBS1L-MYB SNPs, and an SNP upstream of (G)gamma-globin (HBG2; the XmnI polymorphism), in two independent SCD cohorts: the African American Cooperative Study of Sickle Cell Disease (CSSCD) and an SCD cohort from Brazil. We studied the effect of these SNPs on HbF levels and on a measure of SCD-related morbidity (pain crisis rate). We strongly replicated the association between these SNPs and HbF level variation (in the CSSCD, P values range from 0.04 to 2 x 10(-42)). Together, common SNPs at the BCL11A, HBS1L-MYB, and beta-globin (HBB) loci account for >20% of the variation in HbF levels in SCD patients. We also have shown that HbF-associated SNPs associate with pain crisis rate in SCD patients. These results provide a clear example of inherited common sequence variants modifying the severity of a monogenic disease.Sickle cell disease (SCD) is a debilitating monogenic blood disorder with a highly variable phenotype characterized by severe pain crises, acute clinical events, and early mortality. Interindividual variation in fetal hemoglobin (HbF) expression is a known and potentially heritable modifier of SCD severity. High HbF levels are correlated with reduced morbidity and mortality. Common single nucleotide polymorphisms (SNPs) at the BCL11A and HBS1L-MYB loci have been implicated previously in HbF level variation in nonanemic European populations. We recently demonstrated an association between a BCL11A SNP and HbF levels in one SCD cohort [Uda M, et al. (2008) Proc Natl Acad Sci USA 105:1620-1625]. Here, we genotyped additional BCL11A SNPs, HBS1L-MYB SNPs, and an SNP upstream of (G)gamma-globin (HBG2; the XmnI polymorphism), in two independent SCD cohorts: the African American Cooperative Study of Sickle Cell Disease (CSSCD) and an SCD cohort from Brazil. We studied the effect of these SNPs on HbF levels and on a measure of SCD-related morbidity (pain crisis rate). We strongly replicated the association between these SNPs and HbF level variation (in the CSSCD, P values range from 0.04 to 2 x 10(-42)). Together, common SNPs at the BCL11A, HBS1L-MYB, and beta-globin (HBB) loci account for >20% of the variation in HbF levels in SCD patients. We also have shown that HbF-associated SNPs associate with pain crisis rate in SCD patients. These results provide a clear example of inherited common sequence variants modifying the severity of a monogenic disease. |
| Author | Uda, Manuela Cao, Antonio Sanna, Serena Sankaran, Vijay G Bezerra, Marcos André C Araújo, Aderson S Costa, Fernando F Lettre, Guillaume Orkin, Stuart H Schlessinger, David Hirschhorn, Joel N |
| Author_xml | – sequence: 1 givenname: Guillaume surname: Lettre fullname: Lettre, Guillaume email: lettre@broad.mit.edu organization: Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. lettre@broad.mit.edu – sequence: 2 givenname: Vijay G surname: Sankaran fullname: Sankaran, Vijay G – sequence: 3 givenname: Marcos André C surname: Bezerra fullname: Bezerra, Marcos André C – sequence: 4 givenname: Aderson S surname: Araújo fullname: Araújo, Aderson S – sequence: 5 givenname: Manuela surname: Uda fullname: Uda, Manuela – sequence: 6 givenname: Serena surname: Sanna fullname: Sanna, Serena – sequence: 7 givenname: Antonio surname: Cao fullname: Cao, Antonio – sequence: 8 givenname: David surname: Schlessinger fullname: Schlessinger, David – sequence: 9 givenname: Fernando F surname: Costa fullname: Costa, Fernando F – sequence: 10 givenname: Joel N surname: Hirschhorn fullname: Hirschhorn, Joel N – sequence: 11 givenname: Stuart H surname: Orkin fullname: Orkin, Stuart H |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/18667698$$D View this record in MEDLINE/PubMed |
| BookMark | eNpNkD1PwzAQhi1URGlhZkOemJpyduLEHtvyUaQCAzAwRXZyIQHngzgF9U_wmwnQSkzve3fPvTrdiAyqukJCThhMGUT-eVNpNwUJQaQUA7FHDhko5oWBgsE_PyQj514BQAkJB2TIZBhGoZKH5Ovibkab2m7Kum3ywpWO6o52OdL5YsXYbEKX8we28m6f5xOqq5Qa7LT3YmtTVNTWSUG1c73oDuln0eU06-eW5ljWOwg_0Lrf3Ub3ddIWDh3tnSuSN4s0QWtp2je1wyOyn2nr8HirY_J0dfm4WHqr--ubxWzlJYJHncd4BD4DA1oGjEvDNCaKoZKMZ8iZEVxBKvw0E6EOhI_GCKlSTND4EICUfEzO_nKbtn5fo-visnA_h-gK67WLQxUEMpRBD55uwbUpMY2btih1u4l3H-Tfyp10Zg |
| CitedBy_id | crossref_primary_10_1182_blood_2010_11_316893 crossref_primary_10_1177_15353702211028195 crossref_primary_10_1159_000511342 crossref_primary_10_3390_ijms25105427 crossref_primary_10_1016_j_retram_2022_103335 crossref_primary_10_1007_s00438_017_1377_2 crossref_primary_10_1007_s00277_021_04450_x crossref_primary_10_1111_j_1537_2995_2009_02483_x crossref_primary_10_3109_08880018_2011_616573 crossref_primary_10_3389_fgene_2020_00613 crossref_primary_10_1155_2021_8895020 crossref_primary_10_1038_ng_707 crossref_primary_10_1016_j_bcmd_2017_06_004 crossref_primary_10_1016_j_compbiolchem_2019_04_007 crossref_primary_10_1053_j_seminhematol_2022_12_001 crossref_primary_10_1016_j_jstrokecerebrovasdis_2018_06_004 crossref_primary_10_1002_prca_201500133 crossref_primary_10_1186_s40246_021_00329_0 crossref_primary_10_3109_03630269_2015_1124113 crossref_primary_10_3390_cells13141185 crossref_primary_10_1016_j_hemonc_2016_02_003 crossref_primary_10_1055_s_0041_1733950 crossref_primary_10_1007_s00439_016_1696_0 crossref_primary_10_1186_1479_7364_5_2_79 crossref_primary_10_1016_j_bcmd_2017_06_001 crossref_primary_10_4137_GEI_S2626 crossref_primary_10_1089_gtmb_2014_0310 crossref_primary_10_1002_pbc_27934 crossref_primary_10_1126_science_1169216 crossref_primary_10_1007_s12288_025_02102_y crossref_primary_10_1007_s00277_021_04422_1 crossref_primary_10_7555_JBR_34_20200096 crossref_primary_10_1182_blood_2015_04_638528 crossref_primary_10_1186_s40169_016_0092_7 crossref_primary_10_1590_S0104_59702014000400003 crossref_primary_10_1016_S0140_6736_11_60283_3 crossref_primary_10_1177_1535370216642047 crossref_primary_10_1016_j_jprot_2023_104957 crossref_primary_10_3389_fgene_2015_00251 crossref_primary_10_1016_j_bcmd_2016_04_001 crossref_primary_10_1038_nature08243 crossref_primary_10_1182_blood_2009_08_239517 crossref_primary_10_1177_1535370216636726 crossref_primary_10_1016_S0140_6736_15_01341_0 crossref_primary_10_1007_s11033_013_2732_y crossref_primary_10_1002_sctm_17_0192 crossref_primary_10_1016_j_bcmd_2010_04_002 crossref_primary_10_1007_s12288_020_01270_3 crossref_primary_10_1002_ajmg_c_31529 crossref_primary_10_1089_omi_2015_0124 crossref_primary_10_3109_03630269_2011_615876 crossref_primary_10_1002_pbc_27807 crossref_primary_10_3390_ijerph18105417 crossref_primary_10_1007_s00277_020_04187_z crossref_primary_10_1016_j_hoc_2013_11_009 crossref_primary_10_1038_s41576_019_0134_2 crossref_primary_10_1126_science_1165409 crossref_primary_10_1182_blood_2010_11_317081 crossref_primary_10_1182_bloodadvances_2017005231 crossref_primary_10_1002_ajh_21572 crossref_primary_10_1007_s12265_022_10347_5 crossref_primary_10_1038_jhg_2017_76 crossref_primary_10_1016_j_bcmd_2021_102561 crossref_primary_10_1038_nrg2989 crossref_primary_10_1182_blood_2020006425 crossref_primary_10_1186_1471_2164_15_108 crossref_primary_10_3390_genes14030577 crossref_primary_10_1016_j_ajhg_2017_05_012 crossref_primary_10_1016_j_bcmd_2015_10_004 crossref_primary_10_1016_j_bcmd_2015_02_001 crossref_primary_10_3390_ijms24119527 crossref_primary_10_1089_ars_2023_0348 crossref_primary_10_1016_j_bcmd_2013_03_003 crossref_primary_10_1155_2013_193252 crossref_primary_10_1093_hmg_ddae014 crossref_primary_10_3109_03630269_2013_800823 crossref_primary_10_1177_1178631017721178 crossref_primary_10_1586_17474086_2015_1078235 crossref_primary_10_1016_j_bcmd_2014_07_006 crossref_primary_10_1111_bjh_15871 crossref_primary_10_1182_bloodadvances_2022009558 crossref_primary_10_3390_jcm8111927 crossref_primary_10_1016_j_bcmd_2009_12_009 crossref_primary_10_1007_s12185_022_03523_5 crossref_primary_10_1097_MOH_0000000000000029 crossref_primary_10_1097_MOP_0b013e3283420fd0 crossref_primary_10_1182_blood_2014_01_453167 crossref_primary_10_2217_pgs_15_126 crossref_primary_10_1007_s10528_015_9687_8 crossref_primary_10_1016_j_bcmd_2012_12_005 crossref_primary_10_1038_nrd4051 crossref_primary_10_1186_s40246_020_00283_3 crossref_primary_10_1038_ncomms9382 crossref_primary_10_1182_blood_2016_01_678128 crossref_primary_10_1080_03630269_2016_1253586 crossref_primary_10_1007_s11033_014_3195_5 crossref_primary_10_1056_NEJMra1510865 crossref_primary_10_1007_s00439_009_0770_2 crossref_primary_10_1182_bloodadvances_2017009811 crossref_primary_10_31083_j_fbs1602011 crossref_primary_10_3389_frhem_2024_1468952 crossref_primary_10_1126_science_1211053 crossref_primary_10_1007_s00277_016_2675_1 crossref_primary_10_13005_bpj_2881 crossref_primary_10_4137_EBO_S15364 crossref_primary_10_1111_ahg_12077 crossref_primary_10_1111_j_1365_2141_2008_07532_x crossref_primary_10_1038_pr_2013_227 crossref_primary_10_1097_SPC_0b013e32832c6adb crossref_primary_10_1038_s41581_020_0325_2 crossref_primary_10_1111_j_1749_6632_2010_05821_x crossref_primary_10_1101_gad_1897310 crossref_primary_10_3109_03630269_2013_848365 crossref_primary_10_1038_s10038_022_01079_0 crossref_primary_10_1182_blood_2017_11_814335 crossref_primary_10_1080_03630269_2016_1252386 crossref_primary_10_1080_03630269_2018_1482832 crossref_primary_10_1186_s13023_021_02096_6 crossref_primary_10_1038_s41573_025_01236_y crossref_primary_10_1111_ejh_12204 crossref_primary_10_1007_s00277_012_1671_3 crossref_primary_10_1007_s40291_022_00589_z crossref_primary_10_1007_s00439_023_02610_9 crossref_primary_10_1073_pnas_1619052114 crossref_primary_10_1038_s41588_019_0453_4 crossref_primary_10_3109_03630269_2015_1086880 crossref_primary_10_1080_17474086_2019_1649131 crossref_primary_10_1093_nar_gkab671 crossref_primary_10_3109_10408363_2013_847236 crossref_primary_10_3389_fcell_2021_640060 crossref_primary_10_1371_journal_pone_0004218 crossref_primary_10_1007_s00292_009_1137_0 crossref_primary_10_1126_science_1242088 crossref_primary_10_1002_jcla_22207 crossref_primary_10_1080_17434440_2016_1254038 crossref_primary_10_1097_MPH_0000000000000779 crossref_primary_10_1097_MPH_0000000000001626 crossref_primary_10_3109_03630269_2013_789438 crossref_primary_10_3390_v14122716 crossref_primary_10_1007_s00277_021_04627_4 crossref_primary_10_1111_bjh_17101 crossref_primary_10_1111_bjh_17102 crossref_primary_10_1096_fj_13_246637 crossref_primary_10_1002_ajh_22221 crossref_primary_10_1186_s13104_017_2502_3 crossref_primary_10_1016_j_blre_2021_100823 crossref_primary_10_1182_blood_2009_03_210146 crossref_primary_10_1007_s11033_011_1253_9 crossref_primary_10_1111_j_1365_2141_2012_09061_x crossref_primary_10_1093_hmg_ddw170 crossref_primary_10_1001_jamanetworkopen_2023_37484 crossref_primary_10_1002_ajh_24527 crossref_primary_10_1089_omi_2016_0125 crossref_primary_10_1007_s40259_020_00439_6 crossref_primary_10_1590_S1984_82502014000300022 crossref_primary_10_1111_j_1365_2141_2009_07650_x crossref_primary_10_1016_j_tig_2020_05_006 crossref_primary_10_1016_j_bcmd_2016_11_002 crossref_primary_10_1111_bjh_15038 crossref_primary_10_3233_CH_189004 crossref_primary_10_1002_ajh_24872 crossref_primary_10_1139_O09_048 crossref_primary_10_2217_pgs_2018_0064 crossref_primary_10_1016_j_ymgme_2018_02_003 crossref_primary_10_1186_s13148_020_00987_2 crossref_primary_10_1056_NEJMoa1103070 crossref_primary_10_1515_cclm_2011_748 crossref_primary_10_1111_ejh_12340 crossref_primary_10_3109_03630269_2015_1023897 crossref_primary_10_1586_ehm_12_20 crossref_primary_10_1093_hmg_ddp401 crossref_primary_10_1097_MPH_0b013e31822dcc21 crossref_primary_10_3390_diagnostics12061374 crossref_primary_10_1016_j_cll_2012_04_011 crossref_primary_10_1080_03630269_2020_1811117 crossref_primary_10_1128_MCB_00001_10 crossref_primary_10_1097_MOH_0000000000000640 crossref_primary_10_1002_cbin_11972 crossref_primary_10_1089_gtmb_2010_0235 crossref_primary_10_1111_bjh_14297 crossref_primary_10_2217_pgs_2016_0007 crossref_primary_10_3892_br_2022_1535 crossref_primary_10_3109_03630269_2012_735626 crossref_primary_10_1038_ng_3307 crossref_primary_10_1002_ajh_23811 crossref_primary_10_1128_MCB_00253_20 crossref_primary_10_1371_journal_pone_0092506 crossref_primary_10_1089_omi_2013_0167 crossref_primary_10_1089_omi_2016_0105 crossref_primary_10_1371_journal_pone_0197927 crossref_primary_10_1371_journal_pone_0240632 crossref_primary_10_3109_03630269_2012_717515 crossref_primary_10_1016_j_bcmd_2017_08_014 crossref_primary_10_1002_jcp_26292 crossref_primary_10_1073_pnas_0806633105 crossref_primary_10_3109_03630269_2013_805418 crossref_primary_10_1002_ajh_27164 crossref_primary_10_1093_stmcls_sxae049 crossref_primary_10_1177_1535370216668052 crossref_primary_10_4103_ijmr_IJMR_1153_17 crossref_primary_10_1080_17474086_2016_1255142 crossref_primary_10_1097_MOH_0b013e32835f59ba crossref_primary_10_1111_bjh_15011 crossref_primary_10_3889_oamjms_2023_11435 crossref_primary_10_1007_s00277_019_03783_y crossref_primary_10_1038_s41588_022_01152_6 crossref_primary_10_1002_ajh_22032 crossref_primary_10_1038_s41573_020_0083_7 crossref_primary_10_1093_nar_gkt761 crossref_primary_10_1002_ajh_25421 crossref_primary_10_1182_blood_2013_09_528315 crossref_primary_10_1016_j_hoc_2013_12_002 crossref_primary_10_1371_journal_pone_0129431 crossref_primary_10_1016_j_hoc_2022_12_002 crossref_primary_10_1177_1535370216640385 crossref_primary_10_1016_j_bcmd_2011_08_005 crossref_primary_10_2217_pgs_13_31 crossref_primary_10_4081_hr_2016_6678 crossref_primary_10_1016_j_gde_2015_08_001 crossref_primary_10_1002_cmdc_201000505 crossref_primary_10_1016_j_ypmed_2016_09_003 crossref_primary_10_1016_S2352_3026_23_00096_0 crossref_primary_10_1111_bjh_12650 crossref_primary_10_14423_SMJ_0000000000000976 crossref_primary_10_1002_pbc_30934 crossref_primary_10_1016_j_bcmd_2014_11_010 crossref_primary_10_1111_bjh_17786 crossref_primary_10_1007_s12041_018_0942_8 crossref_primary_10_1038_jhg_2011_12 crossref_primary_10_1186_s12920_015_0120_2 crossref_primary_10_1016_j_bpobgyn_2016_10_012 crossref_primary_10_1016_j_retram_2023_103433 crossref_primary_10_1111_bjh_17663 crossref_primary_10_1002_ajh_23232 crossref_primary_10_1016_j_bcmd_2017_01_011 crossref_primary_10_1182_blood_2013_01_478776 crossref_primary_10_1089_crispr_2021_29120_fur crossref_primary_10_1371_journal_pgen_1009835 crossref_primary_10_1016_j_bcmd_2014_02_005 crossref_primary_10_1586_ehm_09_56 crossref_primary_10_1182_blood_2011_03_325258 crossref_primary_10_1016_j_crvi_2012_09_006 crossref_primary_10_1182_blood_2009_04_146852 crossref_primary_10_3109_03630269_2012_691147 crossref_primary_10_3390_cells11193069 crossref_primary_10_1016_j_ctim_2020_102327 crossref_primary_10_1111_j_1365_2141_2010_08105_x crossref_primary_10_1056_NEJMcibr1809628 crossref_primary_10_1080_03630269_2018_1429281 crossref_primary_10_1186_s12887_020_02187_6 crossref_primary_10_1016_j_mgene_2020_100769 crossref_primary_10_1159_000449120 crossref_primary_10_1111_nyas_13001 crossref_primary_10_1007_s00277_025_06277_2 crossref_primary_10_1016_j_bcmd_2014_11_008 crossref_primary_10_1038_s41598_025_94222_8 crossref_primary_10_1089_hum_2016_037 crossref_primary_10_1182_blood_2011_03_331371 crossref_primary_10_1007_s11883_024_01195_6 crossref_primary_10_1073_pnas_1006774107 crossref_primary_10_1080_03630269_2019_1597732 crossref_primary_10_1182_blood_2016_08_736249 crossref_primary_10_1586_ehm_10_44 crossref_primary_10_1146_annurev_med_091708_162036 crossref_primary_10_1080_17474086_2024_2372322 crossref_primary_10_1038_ng_637 crossref_primary_10_1111_j_1749_6632_2010_05549_x crossref_primary_10_1155_2017_1972429 crossref_primary_10_1016_j_gde_2013_02_006 crossref_primary_10_1016_j_jacc_2019_05_002 crossref_primary_10_1016_j_trsl_2015_01_002 crossref_primary_10_1038_s42003_018_0053_3 crossref_primary_10_1080_03630269_2020_1787178 crossref_primary_10_1038_ng_630 crossref_primary_10_1080_17474086_2022_2041410 crossref_primary_10_1038_ng_3793 crossref_primary_10_1182_blood_2012_06_292078 crossref_primary_10_1002_pbc_22754 crossref_primary_10_1038_mtna_2016_52 crossref_primary_10_1038_s41588_021_00904_0 crossref_primary_10_3233_CH_200951 crossref_primary_10_1177_11779322221115536 crossref_primary_10_52711_0974_360X_2021_00915 crossref_primary_10_1016_j_bcmd_2015_05_006 crossref_primary_10_1016_j_bcmd_2017_05_005 crossref_primary_10_1016_j_genrep_2024_101983 crossref_primary_10_1371_journal_pone_0218078 crossref_primary_10_1111_bjh_13961 crossref_primary_10_1182_blood_2009_05_220921 crossref_primary_10_1038_s41434_020_0153_9 crossref_primary_10_1080_17474086_2017_1395279 crossref_primary_10_1016_j_tig_2022_07_003 crossref_primary_10_1038_emboj_2011_450 crossref_primary_10_4103_0971_5916_184285 crossref_primary_10_1093_hmg_ddy051 crossref_primary_10_3390_cells10102597 crossref_primary_10_1016_j_bcmd_2010_05_006 crossref_primary_10_1016_j_jpain_2018_12_003 crossref_primary_10_1182_blood_2010_08_302703 crossref_primary_10_1002_ajh_23613 crossref_primary_10_1111_j_1548_1425_2010_01276_x crossref_primary_10_1007_s40484_013_0009_z crossref_primary_10_1089_omi_2014_0134 crossref_primary_10_1182_blood_2010_03_274399 crossref_primary_10_1371_journal_pone_0078253 crossref_primary_10_1038_ng1109_1161 crossref_primary_10_1159_000431020 crossref_primary_10_15252_emmm_201910316 crossref_primary_10_3389_fped_2024_1467760 crossref_primary_10_1002_pbc_27615 crossref_primary_10_1093_hmg_ddab004 crossref_primary_10_1002_gepi_22602 crossref_primary_10_1080_03630269_2016_1251453 crossref_primary_10_1186_1471_2350_11_51 crossref_primary_10_1016_j_blre_2022_100983 crossref_primary_10_1038_pr_2015_245 crossref_primary_10_1111_nyas_13024 crossref_primary_10_3390_genes5010051 crossref_primary_10_1182_bloodadvances_2016002303 crossref_primary_10_1097_MOH_0b013e328329d07a crossref_primary_10_2147_PGPM_S351599 crossref_primary_10_1053_j_seminhematol_2020_11_007 crossref_primary_10_1111_ijlh_12927 crossref_primary_10_1182_blood_2009_04_217901 crossref_primary_10_1016_j_prrv_2013_11_003 crossref_primary_10_4081_pr_2011_e17 crossref_primary_10_1093_hmg_ddn289 crossref_primary_10_1002_jcla_24105 crossref_primary_10_1016_j_tig_2010_04_002 crossref_primary_10_1172_JCI71520 crossref_primary_10_1146_annurev_genom_083117_021320 crossref_primary_10_1111_bjh_12507 crossref_primary_10_1056_NEJMra2405260 crossref_primary_10_1111_ijlh_13232 crossref_primary_10_1371_journal_pone_0055709 crossref_primary_10_1111_bjh_19006 crossref_primary_10_1111_j_1749_6632_2010_05574_x crossref_primary_10_3389_fphar_2021_779497 crossref_primary_10_1182_bloodadvances_2021004634 crossref_primary_10_1007_s00216_021_03453_x crossref_primary_10_1080_03630269_2020_1772284 crossref_primary_10_1016_j_ajhg_2025_01_018 crossref_primary_10_3389_fgeed_2020_617780 crossref_primary_10_1089_omi_2017_0058 crossref_primary_10_1016_j_bcmd_2015_01_001 crossref_primary_10_1016_j_omtm_2016_12_009 crossref_primary_10_1016_j_bcmd_2014_10_003 crossref_primary_10_1097_MOH_0000000000000333 crossref_primary_10_1016_j_medj_2020_12_011 crossref_primary_10_1038_s41467_022_35508_7 crossref_primary_10_1016_j_banm_2024_03_001 crossref_primary_10_1155_2013_415279 crossref_primary_10_1002_jcla_23945 crossref_primary_10_1093_tropej_fmac073 crossref_primary_10_1182_blood_2011_09_382408 crossref_primary_10_1016_j_ajhg_2017_06_004 crossref_primary_10_1016_S0140_6736_10_61029_X crossref_primary_10_1016_j_tig_2018_09_004 crossref_primary_10_1080_03630269_2018_1463915 crossref_primary_10_1097_MOH_0000000000000579 crossref_primary_10_1182_blood_2020005301 crossref_primary_10_1038_jhg_2012_2 crossref_primary_10_1007_s00277_020_03978_8 crossref_primary_10_1002_iub_226 crossref_primary_10_3390_jpm11060567 crossref_primary_10_1007_s00277_020_04079_2 crossref_primary_10_1111_j_1365_2141_2010_08303_x crossref_primary_10_1007_s00277_018_3536_x crossref_primary_10_1186_s12881_015_0148_3 crossref_primary_10_1007_s40291_019_00386_1 crossref_primary_10_1016_j_leukres_2015_12_001 crossref_primary_10_1016_j_hoc_2010_08_009 crossref_primary_10_1182_blood_2011_07_364190 crossref_primary_10_1016_j_trsl_2014_05_002 crossref_primary_10_1016_j_tracli_2010_05_005 crossref_primary_10_1080_14728222_2022_2066519 crossref_primary_10_1128_MCB_00714_14 crossref_primary_10_1016_j_omtm_2020_03_015 crossref_primary_10_1007_s40291_018_0370_8 |
| ContentType | Journal Article |
| DBID | CGR CUY CVF ECM EIF NPM 7X8 |
| DOI | 10.1073/pnas.0804799105 |
| DatabaseName | Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic |
| DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic |
| DatabaseTitleList | MEDLINE MEDLINE - Academic |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database |
| DeliveryMethod | no_fulltext_linktorsrc |
| Discipline | Sciences (General) |
| EISSN | 1091-6490 |
| ExternalDocumentID | 18667698 |
| Genre | Research Support, Non-U.S. Gov't Journal Article Research Support, N.I.H., Extramural |
| GrantInformation_xml | – fundername: Howard Hughes Medical Institute |
| GroupedDBID | --- -DZ -~X .55 0R~ 123 29P 2AX 2FS 2WC 4.4 53G 5RE 5VS 85S AACGO AAFWJ AANCE AAYJJ ABBHK ABOCM ABPLY ABPPZ ABTLG ABXSQ ABZEH ACGOD ACHIC ACIWK ACNCT ACPRK ADQXQ ADULT ADXHL AENEX AEUPB AEXZC AFFNX AFOSN AFRAH ALMA_UNASSIGNED_HOLDINGS AQVQM AS~ BKOMP CGR CS3 CUY CVF D0L DCCCD DIK DU5 E3Z EBS ECM EIF EJD F5P FRP GX1 H13 HH5 HQ3 HTVGU HYE IPSME JAAYA JBMMH JENOY JHFFW JKQEH JLS JLXEF JPM JSG JST KQ8 L7B LU7 MVM N9A NPM N~3 O9- OK1 P-O PNE PQQKQ R.V RHI RNA RNS RPM RXW SA0 SJN TAE TN5 UKR W8F WH7 WOQ WOW X7M XSW Y6R YBH YKV YSK ZCA ~02 ~KM 7X8 |
| ID | FETCH-LOGICAL-c527t-1270310b0a84128b1aec91e9812fe21b5290d53df56a453ebb589deceb3040882 |
| IEDL.DBID | 7X8 |
| ISICitedReferencesCount | 446 |
| ISICitedReferencesURI | http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000258723800052&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| ISSN | 1091-6490 |
| IngestDate | Fri Sep 05 11:35:30 EDT 2025 Mon Jul 21 06:04:12 EDT 2025 |
| IsDoiOpenAccess | false |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 33 |
| Language | English |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c527t-1270310b0a84128b1aec91e9812fe21b5290d53df56a453ebb589deceb3040882 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| OpenAccessLink | http://doi.org/10.1073/pnas.0804799105 |
| PMID | 18667698 |
| PQID | 69448684 |
| PQPubID | 23479 |
| ParticipantIDs | proquest_miscellaneous_69448684 pubmed_primary_18667698 |
| PublicationCentury | 2000 |
| PublicationDate | 2008-08-19 |
| PublicationDateYYYYMMDD | 2008-08-19 |
| PublicationDate_xml | – month: 08 year: 2008 text: 2008-08-19 day: 19 |
| PublicationDecade | 2000 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States |
| PublicationTitle | Proceedings of the National Academy of Sciences - PNAS |
| PublicationTitleAlternate | Proc Natl Acad Sci U S A |
| PublicationYear | 2008 |
| References | 7517723 - Blood. 1994 Jul 15;84(2):643-9 16554528 - N Engl J Med. 2006 Mar 23;354(12):1264-72 18245381 - Proc Natl Acad Sci U S A. 2008 Feb 5;105(5):1620-5 17701901 - Am J Hum Genet. 2007 Sep;81(3):559-75 8528252 - Nat Genet. 1996 Jan;12(1):58-64 18695233 - Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):11595-6 18367739 - N Engl J Med. 2008 Mar 27;358(13):1362-9 18391951 - Nat Genet. 2008 May;40(5):609-15 7993409 - N Engl J Med. 1994 Jun 9;330(23):1639-44 12717432 - Nat Immunol. 2003 Jun;4(6):525-32 18195334 - Ann Intern Med. 2008 Jan 15;148(2):94-101 4063531 - Blood. 1985 Dec;66(6):1463-5 9585587 - Am J Hum Genet. 1998 Jun;62(6):1468-74 4008590 - J Chronic Dis. 1985;38(6):495-505 17592125 - Proc Natl Acad Sci U S A. 2007 Jul 3;104(27):11346-51 9287233 - N Engl J Med. 1997 Sep 11;337(11):762-9 18391952 - Nat Genet. 2008 May;40(5):575-83 2580306 - Proc Natl Acad Sci U S A. 1985 Apr;82(7):2111-4 17325259 - Diabetes. 2007 May;56(5):1460-7 18354102 - N Engl J Med. 2008 Mar 20;358(12):1240-9 17712044 - Blood. 2007 Nov 15;110(10):3624-6 18193043 - Nat Genet. 2008 Feb;40(2):161-9 18391950 - Nat Genet. 2008 May;40(5):584-91 17767159 - Nat Genet. 2007 Oct;39(10):1197-9 16934002 - PLoS Genet. 2006 Aug 25;2(8):e132 11719382 - Blood. 2001 Dec 1;98(12):3413-20 18193044 - Nat Genet. 2008 Feb;40(2):189-97 1710777 - N Engl J Med. 1991 Jul 4;325(1):11-6 |
| References_xml | – reference: 7517723 - Blood. 1994 Jul 15;84(2):643-9 – reference: 18354102 - N Engl J Med. 2008 Mar 20;358(12):1240-9 – reference: 7993409 - N Engl J Med. 1994 Jun 9;330(23):1639-44 – reference: 17325259 - Diabetes. 2007 May;56(5):1460-7 – reference: 9585587 - Am J Hum Genet. 1998 Jun;62(6):1468-74 – reference: 18193044 - Nat Genet. 2008 Feb;40(2):189-97 – reference: 8528252 - Nat Genet. 1996 Jan;12(1):58-64 – reference: 18193043 - Nat Genet. 2008 Feb;40(2):161-9 – reference: 16934002 - PLoS Genet. 2006 Aug 25;2(8):e132 – reference: 18195334 - Ann Intern Med. 2008 Jan 15;148(2):94-101 – reference: 12717432 - Nat Immunol. 2003 Jun;4(6):525-32 – reference: 18391951 - Nat Genet. 2008 May;40(5):609-15 – reference: 1710777 - N Engl J Med. 1991 Jul 4;325(1):11-6 – reference: 17767159 - Nat Genet. 2007 Oct;39(10):1197-9 – reference: 9287233 - N Engl J Med. 1997 Sep 11;337(11):762-9 – reference: 18391950 - Nat Genet. 2008 May;40(5):584-91 – reference: 2580306 - Proc Natl Acad Sci U S A. 1985 Apr;82(7):2111-4 – reference: 18367739 - N Engl J Med. 2008 Mar 27;358(13):1362-9 – reference: 18391952 - Nat Genet. 2008 May;40(5):575-83 – reference: 11719382 - Blood. 2001 Dec 1;98(12):3413-20 – reference: 17712044 - Blood. 2007 Nov 15;110(10):3624-6 – reference: 18245381 - Proc Natl Acad Sci U S A. 2008 Feb 5;105(5):1620-5 – reference: 16554528 - N Engl J Med. 2006 Mar 23;354(12):1264-72 – reference: 4008590 - J Chronic Dis. 1985;38(6):495-505 – reference: 17701901 - Am J Hum Genet. 2007 Sep;81(3):559-75 – reference: 4063531 - Blood. 1985 Dec;66(6):1463-5 – reference: 17592125 - Proc Natl Acad Sci U S A. 2007 Jul 3;104(27):11346-51 – reference: 18695233 - Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):11595-6 |
| SSID | ssj0009580 |
| Score | 2.4807222 |
| Snippet | Sickle cell disease (SCD) is a debilitating monogenic blood disorder with a highly variable phenotype characterized by severe pain crises, acute clinical... |
| SourceID | proquest pubmed |
| SourceType | Aggregation Database Index Database |
| StartPage | 11869 |
| SubjectTerms | Adolescent Anemia, Sickle Cell - complications Anemia, Sickle Cell - epidemiology Anemia, Sickle Cell - genetics Anemia, Sickle Cell - metabolism Carrier Proteins - genetics Carrier Proteins - metabolism Cohort Studies Female Fetal Hemoglobin - genetics Fetal Hemoglobin - metabolism Genes, myb - genetics Genotype Globins - genetics Globins - metabolism Humans Male Nuclear Proteins - genetics Nuclear Proteins - metabolism Pain - complications Pain - epidemiology Pain - genetics Pain - metabolism Polymorphism, Single Nucleotide - genetics |
| Title | DNA polymorphisms at the BCL11A, HBS1L-MYB, and beta-globin loci associate with fetal hemoglobin levels and pain crises in sickle cell disease |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/18667698 https://www.proquest.com/docview/69448684 |
| Volume | 105 |
| WOSCitedRecordID | wos000258723800052&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| hasFullText | |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1LS8QwEA7qevDi-_2agwcF4zZ9pAkIsrsqHtZFUGE9LWma4uLaVrv6M_zNTvoAL-LBS2lpA8NkMvNNJv2GkKNYGIlA2aUY_TT1FTNUxbbXi-8o1-MJRuiya0k_HAzEcCjvZsh58y-MPVbZ-MTSUceZtnvkbS4xkeDCv8jfqO0ZZWurdQONWdLyEMhYmw6H4gflrqi4CCSj3JdOQ-wTeu08VcUZYiU_RHjkBL-jyzLKXC_9T75lslijS-hU5rBCZky6Slbq9VvAcU0yfbJGvi4HHcizCab-qOlx8VqAmgKiQej2-ox1TuGme8_69PapewoqjSEyU0Utfcg4BQyAY1D1xBqwe7mQ4PsJPJvXrPnIHkcqyrG5wmd0TwXKgHdoGC8TA7ZmAHWBaJ08Xl899G5o3ZuB6sANp9QWrBEZRo4SPoa4iCmjJcN5Z25iXBYFrnTiwIuTgCs_8EwUBULGRmPujm4DYf0GmUuz1GwR8AyiIgwZofKkz0Uk0LhdHSXSaB5qnmyTw0bjI7R9K5xKTfZRjBqdb5PNatJGeUXRMbI0fiGXYufPsbtkoToCgsm03COtBFe92Sfz-nM6Lt4PSpPC6-Du9huGRNXx |
| linkProvider | ProQuest |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=DNA+polymorphisms+at+the+BCL11A%2C+HBS1L-MYB%2C+and+beta-globin+loci+associate+with+fetal+hemoglobin+levels+and+pain+crises+in+sickle+cell+disease&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+-+PNAS&rft.au=Lettre%2C+Guillaume&rft.au=Sankaran%2C+Vijay+G&rft.au=Bezerra%2C+Marcos+Andr%C3%A9+C&rft.au=Ara%C3%BAjo%2C+Aderson+S&rft.date=2008-08-19&rft.issn=1091-6490&rft.eissn=1091-6490&rft.volume=105&rft.issue=33&rft.spage=11869&rft_id=info:doi/10.1073%2Fpnas.0804799105&rft.externalDBID=NO_FULL_TEXT |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1091-6490&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1091-6490&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1091-6490&client=summon |