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Compared with sickle cell anemia haplotypes found in patients of African descent, HbF levels in Saudi and Indian patients with the Arab\u2010Indian (AI) haplotype exceed that in any other haplotype by nearly twofold. Genetic association studies have identified some loci associated with high HbF in the AI haplotype but these observations require functional confirmation. Saudi patients with the Benin haplotype have HbF levels almost twice as high as African patients with this haplotype but this difference is unexplained. Hydroxyurea is still the only FDA approved drug for HbF induction in sickle cell disease. While most patients treated with hydroxyurea have an increase in HbF and some clinical improvement, 10 to 20% of adults show little response to this agent. We review the genetic basis of HbF regulation focusing on sickle cell anemia in Saudi Arabia and discuss new drugs that can induce increased levels of HbF.<\/jats:p>","DOI":"10.1002\/ajh.24872","type":"journal-article","created":{"date-parts":[[2017,7,24]],"date-time":"2017-07-24T08:38:39Z","timestamp":1500885519000},"page":"1233-1242","source":"Crossref","is-referenced-by-count":48,"title":["Fetal hemoglobin in sickle cell anemia: The Arab\u2010Indian haplotype and new therapeutic agents"],"prefix":"10.1002","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5384-8764","authenticated-orcid":false,"given":"Alawi H.","family":"Habara","sequence":"first","affiliation":[{"name":"Department of Medicine Boston University School of Medicine Boston Massachusetts 02118"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6835-3839","authenticated-orcid":false,"given":"Elmutaz M.","family":"Shaikho","sequence":"additional","affiliation":[{"name":"Department of Medicine Boston University School of Medicine Boston Massachusetts 02118"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin H.","family":"Steinberg","sequence":"additional","affiliation":[{"name":"Department of Medicine Boston University School of Medicine Boston Massachusetts 02118"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,8,17]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/1535370216636726"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)61029-X"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI89741"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3814"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.637"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1165409"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12920-015-0120-2"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcmd.2016.04.001"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-02-626259"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2015.140749"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2015.04.005"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.24527"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-10-605022"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00247-14"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)01341-0"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1242088"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2010.05574.x"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad3312"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-08-239517"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0711566105"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0111464"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcmd.2012.12.005"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0804799105"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-03-325258"},{"key":"e_1_2_5_26_1","first-page":"269","article-title":"Fetal haemoglobin and \u03b2\u2010globin gene cluster haplotypes among sickle cell patients in Chhattisgarh","volume":"7","author":"Bhagat S","year":"2013","journal-title":"J Clin Diagn Res."},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.2830440214"},{"key":"e_1_2_5_28_1","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1182\/blood.V85.4.1111.bloodjournal8541111","article-title":"An analysis of fetal hemoglobin variation in sickle cell disease: the relative contributions of the X\u2010linked factor, beta\u2010globin haplotypes, alpha\u2010globin gene number, gender, and age","volume":"85","author":"Chang Y","year":"1995","journal-title":"Blood."},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.707"},{"key":"e_1_2_5_30_1","first-page":"1480","article-title":"The prevalence of sickle cell disease in Saudi children and adolescents. 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