{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T03:33:21Z","timestamp":1780544001140,"version":"3.54.1"},"reference-count":94,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,6,2]],"date-time":"2022-06-02T00:00:00Z","timestamp":1654128000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003093","name":"Ministry of Higher Education Malaysia for Fundamental Research Grant Scheme","doi-asserted-by":"publisher","award":["FRGS\/1\/2019\/SKK06\/USM\/02\/8"],"award-info":[{"award-number":["FRGS\/1\/2019\/SKK06\/USM\/02\/8"]}],"id":[{"id":"10.13039\/501100003093","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Anemia is a condition in which red blood cells and\/or hemoglobin (Hb) concentrations are decreased below the normal range, resulting in a lack of oxygen being transported to tissues and organs. Those afflicted with this condition may feel lethargic and weak, which reduces their quality of life. The condition may be manifested in inherited blood disorders, such as thalassemia and sickle cell disease, whereas acquired disorders include aplastic anemia, chronic disease, drug toxicity, pregnancy, and nutritional deficiency. The augmentation of fetal hemoglobin (HbF) results in the reduction in clinical symptoms in beta-hemoglobinopathies. Several transcription factors as well as medications such as hydroxyurea may help red blood cells produce more HbF. HbF expression increases with the downregulation of three main quantitative trait loci, namely, the XMN1-HBG2, HBS1L-MYB, and BCL11A genes. These genes contain single nucleotide polymorphisms (SNPs) that modulate the expression of HbF differently in various populations. Allele discrimination is important in SNP genotyping and is widely applied in many assays. In conclusion, the expression of HbF with a genetic modifier is crucial in determining the severity of anemic diseases, and genetic modification of HbF expression may offer clinical benefits in diagnosis and disease management.<\/jats:p>","DOI":"10.3390\/diagnostics12061374","type":"journal-article","created":{"date-parts":[[2022,6,2]],"date-time":"2022-06-02T11:05:02Z","timestamp":1654167902000},"page":"1374","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Single Nucleotide Polymorphisms in XMN1-HBG2, HBS1L-MYB, and BCL11A and Their Relation to High Fetal Hemoglobin Levels That Alleviate Anemia"],"prefix":"10.3390","volume":"12","author":[{"given":"Siti Nur Nabeela A\u2019ifah","family":"Mohammad","sequence":"first","affiliation":[{"name":"Department of Haematology, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salfarina","family":"Iberahim","sequence":"additional","affiliation":[{"name":"Department of Haematology, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia"},{"name":"Transfusion Medicine Unit, Hospital Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3878-208X","authenticated-orcid":false,"given":"Wan Suriana","family":"Wan Ab Rahman","sequence":"additional","affiliation":[{"name":"Transfusion Medicine Unit, Hospital Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia"},{"name":"School of Dental Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4975-2038","authenticated-orcid":false,"given":"Mohd Nazri","family":"Hassan","sequence":"additional","affiliation":[{"name":"Department of Haematology, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia"},{"name":"Transfusion Medicine Unit, Hospital Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3379-6063","authenticated-orcid":false,"given":"Hisham Atan","family":"Edinur","sequence":"additional","affiliation":[{"name":"School of Health Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8320-9787","authenticated-orcid":false,"given":"Maryam","family":"Azlan","sequence":"additional","affiliation":[{"name":"School of Health Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2029-2234","authenticated-orcid":false,"given":"Zefarina","family":"Zulkafli","sequence":"additional","affiliation":[{"name":"Department of Haematology, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia"},{"name":"Transfusion Medicine Unit, Hospital Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1056\/NEJMra041809","article-title":"Anemia of Chronic Disease","volume":"352","author":"Weiss","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000452104","article-title":"Anaemia of Chronic Disease: An In-Depth Review","volume":"26","author":"Madu","year":"2017","journal-title":"Med Princ. Pract."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1111\/nyas.14092","article-title":"Anemia epidemiology, pathophysiology, and etiology in low- and middle-income countries","volume":"1450","author":"Chaparro","year":"2019","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1053\/j.seminhematol.2015.07.006","article-title":"Anemia in Clinical Practice-Definition and Classification: Does Hemoglobin Change with Aging?","volume":"52","author":"Motta","year":"2015","journal-title":"Semin. Hematol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4627","DOI":"10.3748\/wjg.15.4627","article-title":"Classification of anemia for gastroenterologists","volume":"15","author":"Chulilla","year":"2009","journal-title":"World J. Gastroenterol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1182\/blood-2011-03-325258","article-title":"Fetal hemoglobin in sickle cell anemia","volume":"118","author":"Akinsheye","year":"2011","journal-title":"Blood"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1111\/j.1365-2141.2009.07650.x","article-title":"Discovering the genetics underlying foetal haemoglobin production in adults","volume":"145","author":"Thein","year":"2009","journal-title":"Br. J. Haematol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1111\/ijlh.12094","article-title":"Interpreting elevated fetal hemoglobin in pathology and health at the basic laboratory level: New and known \u03b3- gene mutations associated with hereditary persistence of fetal hemoglobin","volume":"36","author":"Amato","year":"2014","journal-title":"Int. J. Lab. Hematol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1093\/hmg\/ddp401","article-title":"Control of fetal hemoglobin: New insights emerging from genomics and clinical implications","volume":"18","author":"Thein","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Fanis, P., Kousiappa, I., Phylactides, M., and Kleanthous, M. (2014). Genotyping of BCL11A and HBS1L-MYB SNPs associated with fetal haemoglobin levels: A SNaPshot minisequencing approach. BMC Genom., 15.","DOI":"10.1186\/1471-2164-15-108"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Zakaria, N., Islam, A., Abdullah, W., Bahar, R., Yusoff, A.M., Wahab, R.A., Shamsuddin, S., and Johan, M. (2021). Epigenetic Insights and Potential Modifiers as Therapeutic Targets in \u03b2\u2013Thalassemia. Biomolecules, 11.","DOI":"10.3390\/biom11050755"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-1-60327-411-1_1","article-title":"SNPs: Impact on gene function and phenotype","volume":"578","author":"Shastry","year":"2009","journal-title":"Methods Mol. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1097\/01.MXE.0000415225.85003.47","article-title":"Genetic polymorphism studies in humans","volume":"1","author":"Ismail","year":"2012","journal-title":"Middle East J. Med. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Sukhumsirichart, W. (2018). Polymorphisms. Genetic Diversity and Disease Susceptibility, BoD. Available online: http:\/\/www.intechopen.com\/books\/genetic-diversity-and-disease-susceptibility\/polymorphisms.","DOI":"10.5772\/intechopen.76728"},{"key":"ref_15","first-page":"2","article-title":"Single Nucleotide Polymorphism Genotyping Using BeadChip Microarrays","volume":"78","author":"Lambert","year":"2013","journal-title":"Curr. Protoc. Hum. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1007\/s12024-007-0018-1","article-title":"STRs vs. SNPs: Thoughts on the future of forensic DNA testing","volume":"3","author":"Butler","year":"2007","journal-title":"Forensic Sci. Med. Pathol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Teama, S. (2018). DNA Polymorphisms: DNA-Based Molecular Markers and Their Application in Medicine. Genetic Diversity and Disease Susceptibility, BoD. Available online: https:\/\/www.intechopen.com\/chapters\/62578.","DOI":"10.5772\/intechopen.79517"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.3389\/fgene.2019.01406","article-title":"Single-Nucleotide Polymorphisms (SNP) Mining and Their Effect on the Tridimensional Protein Structure Prediction in a Set of Immunity-Related Expressed Sequence Tags (EST) in Atlantic Salmon (Salmo salar)","volume":"10","author":"Maisey","year":"2020","journal-title":"Front. Genet."},{"key":"ref_19","first-page":"51","article-title":"Fetal hemoglobin during infancy and in sickle cell adults","volume":"6","author":"Edoh","year":"2006","journal-title":"Afr. Health Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3331","DOI":"10.1007\/s11033-014-3195-5","article-title":"Association of Xmn1 \u2212158 \u03b3G variant with severity and HbF levels in \u03b2-thalassemia major and sickle cell anaemia","volume":"41","author":"Dadheech","year":"2014","journal-title":"Mol. Biol. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.bcmd.2017.06.001","article-title":"Molecular basis of \u03b2 thalassemia and potential therapeutic targets","volume":"70","author":"Thein","year":"2018","journal-title":"Blood Cells Mol. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1182\/bloodadvances.2017009811","article-title":"G(HbF): A genetic model of fetal hemoglobin in sickle cell disease","volume":"2","author":"Gardner","year":"2018","journal-title":"Blood Adv."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1179\/1607845414Y.0000000203","article-title":"HbF in HbE\/\u03b2-thalassemia: A clinical and laboratory correlation","volume":"20","author":"Lim","year":"2014","journal-title":"Hematology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4935","DOI":"10.1182\/blood-2010-11-317081","article-title":"A 3-bp deletion in the HBS1L-MYB intergenic region on chromosome 6q23 is associated with HbF expression","volume":"117","author":"Farrell","year":"2011","journal-title":"Blood"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"133","DOI":"10.3329\/bmrcb.v45i3.44642","article-title":"Role of XmnI polymorphism in HbF induction in HbE\/\u03b2 and \u03b2-thalassaemia patients","volume":"45","author":"Hossain","year":"2019","journal-title":"Bangladesh Med. Res. Counc. Bull."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.hemonc.2017.09.003","article-title":"Hereditary persistence of hemoglobin F is protective against red cell sickling. A case report and brief review","volume":"12","author":"Sokolova","year":"2019","journal-title":"Hematol. Oncol. Stem Cell Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/S0950-3536(05)80070-8","article-title":"7 Increased HbF in adult life","volume":"6","author":"Wood","year":"1993","journal-title":"Bailli\u00e8re\u2019s Clin. Haematol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Fitzhugh, C.D., Hsieh, M.M., Allen, D., Coles, W.A., Seamon, C., Ring, M., Zhao, X., Minniti, C.P., Rodgers, G.P., and Schechter, A.N. (2015). Hydroxyurea-Increased Fetal Hemoglobin Is Associated with Less Organ Damage and Longer Survival in Adults with Sickle Cell Anemia. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0141706"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1111\/bjh.14463","article-title":"Elevated fetal haemoglobin is a predictor of better outcome in MDS\/AML patients receiving 5-aza-2\u2032-deoxycytidine (Decitabine)","volume":"176","author":"Ihorst","year":"2017","journal-title":"Br. J. Haematol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1586\/17474086.2015.1078235","article-title":"A Systematic Review of Known Mechanisms of Hydroxyurea-induced Foetal Haemoglobin for Treatment of Sickle Cell Disease","volume":"8","author":"Pule","year":"2015","journal-title":"Expert Rev. Hematol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1016\/j.clinbiochem.2009.06.023","article-title":"The relevance of hemoglobin F measurement in the diagnosis of thalassemias and related hemoglobinopathies","volume":"42","author":"Mosca","year":"2009","journal-title":"Clin. Biochem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e171","DOI":"10.1097\/MPH.0000000000000779","article-title":"Relationship between Some Single-nucleotide Polymorphism and Response to Hydroxyurea Therapy in Iranian Patients with \u03b2-Thalassemia Intermedia","volume":"39","author":"Karimi","year":"2017","journal-title":"J. Pediatr. Hematol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"5300","DOI":"10.1182\/blood-2009-04-146852","article-title":"How I use hydroxyurea to treat young patients with sickle cell anemia","volume":"115","author":"Ware","year":"2010","journal-title":"Blood"},{"key":"ref_34","first-page":"5","article-title":"Pharmacogenomics of the Drugs used for the Treatment of Thalassemia","volume":"6","author":"Panja","year":"2015","journal-title":"J. Cytol. Histol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"146","DOI":"10.3109\/21691401.2016.1138487","article-title":"Modulation of microRNAs expression in hematopoietic stem cells treated with sodium butyrate in inducing fetal hemoglobin expression","volume":"45","author":"Tayebi","year":"2016","journal-title":"Artif. Cells Nanomed. Biotechnol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2864","DOI":"10.1182\/blood-2007-01-065201","article-title":"Thalidomide induces \u03b3-globin gene expression through increased reactive oxygen species\u2013mediated p38 MAPK signaling and histone H4 acetylation in adult erythropoiesis","volume":"110","author":"Aerbajinai","year":"2007","journal-title":"Blood"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3959","DOI":"10.3389\/fphar.2021.814302","article-title":"Investigating the Efficacy and Safety of Thalidomide for Treating Patients With \u00df-Thalassemia: A Meta-Analysis","volume":"12","author":"Lu","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.cca.2012.10.002","article-title":"Changes in hemoglobin F levels in pregnant women unaffected by clinical fetomaternal hemorrhage","volume":"415","author":"Yamada","year":"2013","journal-title":"Clin. Chim. Acta"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1639243","DOI":"10.1080\/2331205X.2019.1639243","article-title":"Association of Xmn1 polymorphism and consanguineous marriage with fetal hemoglobin in Syrian patients with sickle cell disease","volume":"6","author":"Kahhaleh","year":"2019","journal-title":"Cogent Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e25","DOI":"10.1111\/ijlh.12273","article-title":"Analysis of theXmn1-G\u03b3 polymorphism in \u03b2-thalassemia\/hemoglobin E (HbE) and homozygous HbE patients with low and high levels of HbF","volume":"37","author":"Prasing","year":"2015","journal-title":"Int. J. Lab. Hematol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.hemonc.2016.02.003","article-title":"Modifying effect of XmnI, BCL11A, and HBS1L-MYB on clinical appearances: A study on \u03b2-thalassemia and hemoglobin E\/\u03b2-thalassemia patients in Indonesia","volume":"9","author":"Rujito","year":"2016","journal-title":"Hematol. Oncol. Stem Cell Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.phoj.2020.04.001","article-title":"Factors affecting health-related quality of life and its association with the Xmn1-G\u03b3 polymorphism among adolescents with transfusion-dependent beta thalassemia and HbE\/\u03b2-thalassemia in East Coast Malaysia","volume":"5","author":"Yusof","year":"2020","journal-title":"Pediatr. Hematol. Oncol. J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1111\/j.1751-553X.2012.01405.x","article-title":"Molecular study and genotype\/phenotype correlation of \u03b2 thalassemia in Malaysia","volume":"34","author":"Sivalingam","year":"2012","journal-title":"Int. J. Lab. Hematol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1002\/pbc.22754","article-title":"Genetic modifiers of HbF and response to hydroxyurea in sickle cell disease","volume":"56","author":"Green","year":"2011","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"11869","DOI":"10.1073\/pnas.0804799105","article-title":"DNA polymorphisms at the BCL11A, HBS1L-MYB, and-globin loci associate with fetal hemoglobin levels and pain crises in sickle cell disease","volume":"105","author":"Lettre","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"932306","DOI":"10.1155\/2014\/932306","article-title":"Thalassemia and Hemoglobin E in Southern Thai Blood Donors","volume":"2014","author":"Nuinoon","year":"2014","journal-title":"Adv. Hematol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.3324\/haematol.2011.046748","article-title":"Variants in genetic modifiers of \u03b2-Thalassemia can help to predict the major or intermedia type of the disease","volume":"96","author":"Badens","year":"2011","journal-title":"Haematologica"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.bcmd.2008.09.002","article-title":"Molecular, hematological and clinical aspects of thalassemia major and thalassemia intermedia associated with Hb E-\u03b2-thalassemia in Northeast Thailand","volume":"42","author":"Nuntakarn","year":"2009","journal-title":"Blood Cells Mol. Dis."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Allard, P., Alhaj, N., Lobitz, S., Cario, H., Jarisch, A., Grosse, R., Oevermann, L., Hakimeh, D., Tagliaferri, L., and Kohne, E. (2021). Genetic modifiers of fetal hemoglobin affect the course of sickle cell disease in patients treated with hydroxyurea. Haematologica, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/34706496\/.","DOI":"10.3324\/haematol.2021.278952"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/0028-2243(95)02105-2","article-title":"High HbF in pregnancy is associated with the Xmn I polymorphism at the-158bp of the Gq,-globin gene","volume":"60","author":"Lolis","year":"1995","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"627","DOI":"10.48048\/wjst.2018.3151","article-title":"Genotyping of BCL11A and HBS1L-MYB Single Nucleotide Polymorphisms in \u03b2-thalassemia\/HbE and Homozygous HbE Subjects with Low and High Levels of HbF","volume":"15","author":"Prasing","year":"2018","journal-title":"Walailak J. Sci. Technol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1080\/10245332.2015.1107275","article-title":"rs11886868 and rs4671393 of BCL11A associated with HbF level variation and modulate clinical events among sickle cell anemia patients","volume":"21","author":"Chaouch","year":"2016","journal-title":"Hematology"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2673","DOI":"10.1007\/s00277-019-03783-y","article-title":"Genetic modulators of fetal hemoglobin expression and ischemic stroke occurrence in African descendant children with sickle cell anemia","volume":"98","author":"Nicolau","year":"2019","journal-title":"Ann. Hematol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"449","DOI":"10.4103\/0971-5916.184285","article-title":"Association of BCL11A genetic variant (Rs11886868) with severityin \u03b2-thalassaemia major & sickle cell anaemia","volume":"143","author":"Dadheech","year":"2016","journal-title":"Indian J. Med. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1101\/gad.1897310","article-title":"Transcriptional silencing of \u03b3-globin by BCL11A involves long-range interactions and cooperation with SOX6","volume":"24","author":"Xu","year":"2010","journal-title":"Genes Dev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3945","DOI":"10.1182\/blood-2010-11-316893","article-title":"Transcriptional regulation of fetal to adult hemoglobin switching: New therapeutic opportunities","volume":"117","author":"Wilber","year":"2011","journal-title":"Blood"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2279","DOI":"10.1007\/s00277-020-04187-z","article-title":"Association between BCL11A, HSB1L-MYB, and XmnI \u03b3G-158 (C\/T) gene polymorphism and hemoglobin F level in Egyptian sickle cell disease patients","volume":"99","author":"Yassa","year":"2020","journal-title":"Ann. Hematol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.bcmd.2016.11.002","article-title":"The role of BCL11A and HMIP-2 polymorphisms on endogenous and hydroxyurea induced levels of fetal hemoglobin in sickle cell anemia patients from southern Brazil","volume":"62","author":"Friedrisch","year":"2016","journal-title":"Blood Cells Mol. Dis."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.1073\/pnas.0711566105","article-title":"Genome-wide association study shows BCL11A associated with persistent fetal hemoglobin and amelioration of the phenotype of-thalassemia","volume":"105","author":"Uda","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_60","first-page":"3624","article-title":"The HBS1L-MYB intergenic region on chromosome 6q23.3 influences erythrocyte, platelet, and monocyte counts in humans","volume":"105","author":"Menzel","year":"2007","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Adeyemo, T.A., Ojewunmi, O.O., Oyetunji, I.A., Rooks, H., Rees, D.C., Akinsulie, A.O., Akanmu, A.S., Thein, S.L., and Menzel, S. (2018). A survey of genetic fetal-haemoglobin modifiers in Nigerian patients with sickle cell anaemia. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0197927"},{"key":"ref_62","first-page":"28","article-title":"Genetic Variants in HBS1L-MYB rs9399137 and rs11759553 Associated with Elevated HbF Levels Among Filipino \u03b2\u00b0-deletion Carriers","volume":"2","author":"The","year":"2017","journal-title":"J. Biomed. Clin. Sci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"100769","DOI":"10.1016\/j.mgene.2020.100769","article-title":"Genetic variants of HBS1L-MYB with Hb subtypes level among Filipino \u03b2\u00b0-deletion carriers co-inherited with \u2212\u03b13.7 deletion thalassaemia","volume":"26","author":"Lim","year":"2020","journal-title":"Meta Gene"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"696","DOI":"10.3324\/haematol.2012.074492","article-title":"Hydroxyurea responsiveness in \u03b2-thalassemic patients is determined by the stress response adaptation of erythroid progenitors and their differentiation propensity","volume":"98","author":"Pourfarzad","year":"2013","journal-title":"Haematologica"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/sj.ki.5001608","article-title":"Prevalence of complications in children with chronic kidney disease according to KDOQI","volume":"70","author":"Wong","year":"2006","journal-title":"Kidney Int."},{"key":"ref_66","first-page":"1394","article-title":"Modulatory effect of single nucleotide polymorphism in Xmn1, BCL11A and HBS1L-MYB loci on foetal haemoglobin levels in \u03b2-thalassemia major and Intermedia patients","volume":"71","author":"Bashir","year":"2021","journal-title":"J. Pak. Med. Assoc."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1172\/JCI71520","article-title":"HBS1L-MYB intergenic variants modulate fetal hemoglobin via long-range MYB enhancers","volume":"124","author":"Stadhouders","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1007\/s12185-008-0167-3","article-title":"Association of SNP in exon 1 of HBS1L with hemoglobin F level in \u03b20-thalassemia\/hemoglobin E","volume":"88","author":"Pandit","year":"2008","journal-title":"Int. J. Hematol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1136\/jmg.2008.060335","article-title":"The HBS1L-MYB intergenic region on chromosome 6q23 is a quantitative trait locus controlling fetal haemoglobin level in carriers of beta-thalassaemia","volume":"45","author":"So","year":"2008","journal-title":"J. Med. Genet."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1182\/blood-2006-01-008912","article-title":"cMYB is involved in the regulation of fetal hemoglobin production in adults","volume":"108","author":"Jiang","year":"2006","journal-title":"Blood"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"11346","DOI":"10.1073\/pnas.0611393104","article-title":"Intergenic variants of HBS1L-MYB are responsible for a major quantitative trait locus on chromosome 6q23 influencing fetal hemoglobin levels in adults","volume":"104","author":"Thein","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/s40291-018-0370-8","article-title":"Genetic Modifiers of Fetal Haemoglobin in Sickle Cell Disease","volume":"23","author":"Menzel","year":"2018","journal-title":"Mol. Diagnosis Ther."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Beverborg, N.G., Verweij, N., Klip, I.T., van der Wal, H.H., Voors, A.A., van Veldhuisen, D.J., Gansevoort, R.T., Bakker, S.J.L., van der Harst, P., and van der Meer, P. (2015). Erythropoietin in the General Population: Reference Ranges and Clinical, Biochemical and Genetic Correlates. PLoS ONE, 10, Available online: https:\/\/journals.plos.org\/plosone\/article?id=10.1371\/journal.pone.0125215.","DOI":"10.1371\/journal.pone.0125215"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e1696","DOI":"10.1002\/mgg3.1696","article-title":"Hyperhaemolysis in a pregnant woman with a homozygous \u03b20-thalassemia mutation and two genetic modifiers","volume":"9","author":"Jiwu","year":"2021","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/j.cell.2018.03.016","article-title":"Direct Promoter Repression by BCL11A Controls the Fetal to Adult Hemoglobin Switch","volume":"173","author":"Liu","year":"2018","journal-title":"Cell"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1839","DOI":"10.1126\/science.1165409","article-title":"Human Fetal Hemoglobin Expression Is Regulated by the Developmental Stage-Specific Repressor BCL11A","volume":"322","author":"Sankaran","year":"2008","journal-title":"Science"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Shen, Y., Li, R., Teichert, K., Montbleau, K.E., Verboon, J.M., Voit, R.A., and Sankaran, V.G. (2021). Pathogenic BCL11A variants provide insights into the mechanisms of human fetal hemoglobin silencing. PLoS Genet., 17.","DOI":"10.1371\/journal.pgen.1009835"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1038\/ng.637","article-title":"KLF1 regulates BCL11A expression and \u03b3- to \u03b2-globin gene switching","volume":"42","author":"Zhou","year":"2010","journal-title":"Nat. Genet"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/MOP.0b013e3283420fd0","article-title":"Update on fetal hemoglobin gene regulation in hemoglobinopathies","volume":"23","author":"Bauer","year":"2011","journal-title":"Curr. Opin. Pediatr."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2363","DOI":"10.1172\/JCI81163","article-title":"BCL11A deletions result in fetal hemoglobin persistence and neurodevelopmental alterations","volume":"125","author":"Basak","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"305","DOI":"10.3324\/haematol.2012.061994","article-title":"Estimation of the difference in HbF expression due to loss of the 5\u2032 \u03b4-globin BCL11A binding region","volume":"98","author":"Ghedira","year":"2013","journal-title":"Haematologica"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1007\/s12288-020-01270-3","article-title":"Detection of BCL11A and HBS1L-MYB Genotypes in Sickle Cell Anemia","volume":"36","author":"Qadah","year":"2020","journal-title":"Indian J. Hematol. Blood Transfus."},{"key":"ref_83","first-page":"303","article-title":"A genome-wide association identified the common genetic variants influence disease severity in \u03b20-thalassemia\/hemoglobin e","volume":"127","author":"Nuinoon","year":"2010","journal-title":"Qual. Life Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1146\/annurev.bioeng.9.060906.152037","article-title":"SNP genotyping: Technologies and biomedical applications","volume":"9","author":"Kim","year":"2007","journal-title":"Annu. Rev. Biomed. Eng."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Chamouine, A., Saandi, T., Muszlak, M., Larmaraud, J., Lambrecht, L., Poisson, J., Balicchi, J., Pissard, S., and Elenga, N. (2020). High fetal hemoglobin level is associated with increased risk of cerebral vasculopathy in children with sickle cell disease in Mayotte. BMC Pediatr., 20.","DOI":"10.1186\/s12887-020-02187-6"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.ygeno.2012.01.003","article-title":"Development of TaqMan allelic discrimination based genotyping of large DNA deletions","volume":"99","author":"Fedick","year":"2012","journal-title":"Genomics"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1021\/ac061729e","article-title":"Genotyping of Single-Nucleotide Polymorphisms by Primer Extension Reaction in a Dry-Reagent Dipstick Format","volume":"79","author":"Litos","year":"2006","journal-title":"Anal. Chem."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1097\/00062752-200201000-00005","article-title":"Microarrays in hematology","volume":"9","author":"Walker","year":"2002","journal-title":"Curr. Opin. Hematol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1101\/gr.150201","article-title":"Robust and Accurate Single Nucleotide Polymorphism Genotyping by Dynamic Allele-Specific Hybridization (DASH): Design Criteria and Assay Validation","volume":"11","author":"Prince","year":"2001","journal-title":"Genome Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"559","DOI":"10.2144\/000112960","article-title":"Improvements to bead-based oligonucleotide ligation SNP genotyping assays","volume":"45","author":"Bruse","year":"2008","journal-title":"BioTechniques"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"e70","DOI":"10.1093\/nar\/gni069","article-title":"Diagnostic application of padlock probes--multiplex detection of plant pathogens using universal microarrays","volume":"33","author":"Szemes","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/978-1-4939-1966-6_7","article-title":"Genotyping analysis using an RFLP assay","volume":"1245","author":"Dai","year":"2015","journal-title":"Methods Mol. Biol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"e66","DOI":"10.1093\/nar\/gng066","article-title":"Genotyping single nucleotide polymorphisms directly from genomic DNA by invasive cleavage reaction on microspheres","volume":"31","author":"Rao","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.mrfmmm.2004.08.016","article-title":"The Invader\u00ae assay for SNP genotyping","volume":"573","author":"Olivier","year":"2005","journal-title":"Mutat. Res."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/12\/6\/1374\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:23:49Z","timestamp":1760138629000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/12\/6\/1374"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,2]]},"references-count":94,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["diagnostics12061374"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics12061374","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,2]]}}}