{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T03:28:54Z","timestamp":1789874934443,"version":"4.0.1"},"reference-count":45,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2013,5,30]],"date-time":"2013-05-30T00:00:00Z","timestamp":1369872000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2013,7]]},"abstract":"<jats:p>\n                    The recently completed BABY HUG trial investigated the safety and efficacy of hydroxyurea in infants with sickle cell anemia (SCA). To investigate the effects of known genetic modifiers, genomic DNA on 190 randomized subjects were analyzed for alpha thalassemia, beta\u2010globin haplotype, polymorphisms affecting endogenous fetal hemoglobin (HbF) levels (\n                    <jats:italic>XmnI<\/jats:italic>\n                    ,\n                    <jats:italic>BCL11A<\/jats:italic>\n                    , and\n                    <jats:italic>HBS1L\u2010MYB<\/jats:italic>\n                    ),\n                    <jats:italic>UGT1A1<\/jats:italic>\n                    promoter polymorphisms, and the common\n                    <jats:italic>G6PD<\/jats:italic>\n                    A\n                    <jats:sup>\u2212<\/jats:sup>\n                    mutation. At study entry, infants with alpha thalassemia trait had significantly lower mean corpuscular volume, total bilirubin, and absolute reticulocyte count. Beta\u2010globin haplotypes associated with milder disease had significantly higher hemoglobin and %HbF.\n                    <jats:italic>BCL11A<\/jats:italic>\n                    and\n                    <jats:italic>XmnI<\/jats:italic>\n                    polymorphisms had significant effects on baseline HbF, while\n                    <jats:italic>UGT1A1<\/jats:italic>\n                    promoter polymorphisms significantly influenced baseline serum bilirubin. At study exit, subjects randomized to placebo still exhibited laboratory effects of alpha thalassemia and other modifiers, while those assigned hydroxyurea had treatment effects that exceeded most genetic influences. The pain phenotype was influenced by HbF modifiers in both treatment groups. These data document that genetic polymorphisms do modify laboratory and clinical phenotypes even in very young patients with SCA. The hydroxyurea effects are more potent, however, indicating that treatment criteria should not be limited to certain genetic subsets, and supporting the use of hydroxyurea for all young patients with SCA. Am. J. Hematol. 88:571\u2013576, 2013. \u00a9 2013 Wiley Periodicals, Inc.\n                  <\/jats:p>","DOI":"10.1002\/ajh.23457","type":"journal-article","created":{"date-parts":[[2013,4,20]],"date-time":"2013-04-20T04:34:40Z","timestamp":1366432480000},"page":"571-576","source":"Crossref","is-referenced-by-count":77,"title":["Genetic modifiers of sickle cell anemia in the BABY HUG cohort: influence on laboratory and clinical phenotypes"],"prefix":"10.1002","volume":"88","author":[{"given":"Vivien A.","family":"Sheehan","sequence":"first","affiliation":[{"name":"Department of Pediatrics Hematology Center, Baylor College of Medicine Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoyu","family":"Luo","sequence":"additional","affiliation":[{"name":"Clinical Trials and Surveys Corporation Owings Mills Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan M.","family":"Flanagan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Hematology Center, Baylor College of Medicine Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thad A.","family":"Howard","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Hematology Center, Baylor College of Medicine Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce W.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Clinical Trials and Surveys Corporation Owings Mills Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winfred C.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Hematology St. Jude Children's Research Hospital Memphis Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah","family":"Kutlar","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology Georgia Health Sciences Center Augusta Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell E.","family":"Ware","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Hematology Center, Baylor College of Medicine Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"BABY HUG Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,5,30]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V86.2.776.bloodjournal862776"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200001133420203"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2009.06.060"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/00008480-200102000-00004"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/15227950151073138"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V86.11.4382a.bloodjournal86114382a"},{"key":"e_1_2_6_8_1","first-page":"136","article-title":"Osteonecrosis of the humeral head in sickle cell disease","author":"Milner PF","year":"1993","journal-title":"Clin Orthop Relat Res"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198504043121403"},{"key":"e_1_2_6_10_1","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/S0889-8588(18)30426-X","article-title":"Beta s\u2010gene\u2010cluster haplotypes in sickle cell anemia. Clinical and hematologic features","volume":"5","author":"Powars DR","year":"1991","journal-title":"Hematol Oncol Clin North Am"},{"key":"e_1_2_6_11_1","first-page":"55","article-title":"Beta\u2010S gene cluster haplotypes modulate hematologic and hemorheologic expression in sickle cell anemia. Use in predicting clinical severity","volume":"16","author":"Powars DR","year":"1994","journal-title":"Am J Pediatr Hematol Oncol"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.2830360305"},{"key":"e_1_2_6_13_1","first-page":"141","article-title":"A mutation associated with elevated G gamma chain in sickle cell anemia and hereditary persistence of fetal hemoglobin","volume":"191","author":"Gilman JG","year":"1985","journal-title":"Prog Clin Biol Res"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0711566105"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1165409"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0611393104"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/00043426-200110000-00011"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2007.06643.x"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1067\/mlc.2003.28"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-03-143891"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-01-332205"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.21958"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2010.08215.x"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)60355-3"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.22282"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.2214\/AJR.10.4664"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V98.1.250"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.2830320113"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1086\/319501"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.20574"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.1996.284816.x"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1097\/00062752-199502020-00001"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.75.4.1979"},{"key":"e_1_2_6_34_1","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1182\/blood.V71.3.748.748","article-title":"Effects of glucose\u20106\u2010phosphate dehydrogenase deficiency upon sickle cell anemia","volume":"71","author":"Steinberg MH","year":"1988","journal-title":"Blood"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-04-216861"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-02-0521"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-07-364190"},{"key":"e_1_2_6_38_1","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1182\/blood.V66.4.783.783","article-title":"DNA sequence variation associated with elevated fetal G gamma globin production","volume":"66","author":"Gilman JG","year":"1985","journal-title":"Blood"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.82.7.2111"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2011.08937.x"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199202273260905"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.2830450402"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.3109\/03630269.2010.526003"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1097\/00043426-200308000-00007"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.3109\/03630268909003397"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1159\/000320271"}],"container-title":["American Journal of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajh.23457","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajh.23457","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T05:40:07Z","timestamp":1696570807000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajh.23457"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,5,30]]},"references-count":45,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2013,7]]}},"alternative-id":["10.1002\/ajh.23457"],"URL":"https:\/\/doi.org\/10.1002\/ajh.23457","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.718002243.793479051","asserted-by":"object"}]},"ISSN":["0361-8609","1096-8652"],"issn-type":[{"value":"0361-8609","type":"print"},{"value":"1096-8652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,5,30]]}}}