{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T23:26:51Z","timestamp":1788910011471,"version":"build-2803163510"},"reference-count":48,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2016,4,1]],"date-time":"2016-04-01T00:00:00Z","timestamp":1459468800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2016,3,6]],"date-time":"2016-03-06T00:00:00Z","timestamp":1457222400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Ministry of Research, Technology, and Higher Education of Indonesia","award":["1024\/UN.23.10\/PN\/2014"],"award-info":[{"award-number":["1024\/UN.23.10\/PN\/2014"]}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,4]]},"abstract":"<jats:sec>\n                    <jats:title>Objective\/background:<\/jats:title>\n                    <jats:p>\n                      Thalassemia is a monogenic hematologic disease that has the highest prevalence globally. In addition, there is complexity of the genetic background associated with a variety of phenotypes presented among patients. Genetic heterogeneity related to fetal hemoglobin (HbF) production has been reported as an influencing phenotypic factor of \u03b2-thalassemia (\u03b2-thal). Therefore, this study aimed to find the effect of these genetic modifiers, especially in the\n                      <jats:italic toggle=\"yes\">XmnI<\/jats:italic>\n                      locus, rs11886868, rs766432 (\n                      <jats:italic toggle=\"yes\">BCL11A<\/jats:italic>\n                      ), and rs9399137 (\n                      <jats:italic toggle=\"yes\">HBS1LMYB<\/jats:italic>\n                      ), among \u03b2-thal and HbE\/\u03b2-thal patients in Indonesia, according to laboratory and clinical outcomes, including HbF levels and clinical scores. This study was also designed to compare these modifying effects among \u03b2-thal and HbE\/\u03b2-thal patients in Indonesia.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      A total of 189 patients with genotyping of \u03b2-thal and HbE\/\u03b2-thal were included in this study. The erythrocytes index and Hb electrophoresis measurements were calculated using appropriate methods. The severity of \u03b2-thal and HbE\/\u03b2-thal was classified based on the Mahidol score. Polymorphism of the\n                      <jats:italic toggle=\"yes\">XmnI<\/jats:italic>\n                      locus, rs11886868, rs766432 (\n                      <jats:italic toggle=\"yes\">BCL11A<\/jats:italic>\n                      ), and rs9399137 (\n                      <jats:italic toggle=\"yes\">HBS1LMYB<\/jats:italic>\n                      ) was determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and amplification refractory mutation system (ARMS) methods.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      The distributions of minor allele in the\n                      <jats:italic toggle=\"yes\">XmnI<\/jats:italic>\n                      locus, rs11886868, rs766432, and rs9399137 were 14%, 22%, 19% and 18% respectively. The variation allele in the\n                      <jats:italic toggle=\"yes\">XmnI<\/jats:italic>\n                      locus, rs11886868, and rs766432 showed a significant value for modifying HbF and clinical score in HbE\/\u03b2-thal patients, but rs9399137 did not demonstrate such features. In \u03b2-thal patients, however, no correlation was found for any single-nucleotide polymorphisms and clinical appearance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>\n                      The\n                      <jats:italic toggle=\"yes\">XmnI<\/jats:italic>\n                      locus, rs11886868, and rs766432 have a modifying effect on HbF and clinical score in HbE\/\u03b2-thal patients in Indonesia, but not in \u03b2-thal patients.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1016\/j.hemonc.2016.02.003","type":"journal-article","created":{"date-parts":[[2016,3,17]],"date-time":"2016-03-17T16:43:27Z","timestamp":1458233007000},"page":"55-63","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":44,"title":["Modifying effect of XmnI, BCL11A, and HBS1L-MYB on clinical appearances"],"prefix":"10.4103","volume":"9","author":[{"given":"Lantip","family":"Rujito","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Basalamah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wahyu","family":"Siswandari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joko","family":"Setyono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gondo","family":"Wulandari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sri","family":"Mulatsih","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdul Salam M.","family":"Sofro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad Hamim","family":"Sadewa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sutaryo","family":"Sutaryo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"10.1016\/j.hemonc.2016.02.003_b0005","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1111\/j.1749-6632.2010.05546.x","article-title":"Thalassemia as a global health problem: recent progress toward its control in the developing countries","volume":"1202","author":"Weatherall","year":"2010","journal-title":"Ann N Y Acad Sci"},{"key":"10.1016\/j.hemonc.2016.02.003_b0010","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1750-1172-5-11","article-title":"Beta-thalassemia","volume":"5","author":"Galanello","year":"2010","journal-title":"Orphanet J Rare 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Guidelines for the management of transfusion dependent thalassaemia (TDT). 3rd ed. Cappellini MD, Cohen A, Porter J, Taher A, Viprakasit V, editors. Nicosia, Cyprus: Thalassaemia International Federation Publisher; 2014."},{"key":"10.1016\/j.hemonc.2016.02.003_b0090","series-title":"GeneReviews: 1993\u20132016","article-title":"Beta-thalassemia","author":"Cao","year":"2015"},{"key":"10.1016\/j.hemonc.2016.02.003_b0095","series-title":"Factors associated with quality of life in children with beta thalassemia major","author":"Bulan","year":"2009"},{"key":"10.1016\/j.hemonc.2016.02.003_b0100","doi-asserted-by":"crossref","first-page":"244","DOI":"10.14238\/sp13.4.2011.244-9","article-title":"Blood transfusion need on post-splenectomy thalassemia major","volume":"13","author":"Andriastuti","year":"2011","journal-title":"Sari Pediatri"},{"key":"10.1016\/j.hemonc.2016.02.003_b0105","first-page":"380","article-title":"Relationship between hemoglobin pre-transfusion, iron chelating agent and growth among thalassemia major patients","volume":"57","author":"Ermaya","year":"2007","journal-title":"Madjalah Kedokt Indones"},{"key":"10.1016\/j.hemonc.2016.02.003_b0110","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1179\/1607845413Y.0000000110","article-title":"Hepcidin expression from monocyte of splenectomized and non-splenectomized patients with HbE-\u03b2-thalassemia","volume":"19","author":"Pratummo","year":"2014","journal-title":"Hematology"},{"key":"10.1016\/j.hemonc.2016.02.003_b0115","series-title":"The thalassaemia syndromes","author":"Weatherall","year":"2008"},{"key":"10.1016\/j.hemonc.2016.02.003_b0120","doi-asserted-by":"crossref","first-page":"3199","DOI":"10.1182\/blood.V94.9.3199","article-title":"Why are hemoglobin F levels increased in HbE\/\u03b2 thalassemia?","volume":"94","author":"Rees","year":"1999","journal-title":"Blood"},{"key":"10.1016\/j.hemonc.2016.02.003_b0125","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.bcmd.2011.10.003","article-title":"Delayed fetal hemoglobin switching in subjects with KLF1 gene mutation","volume":"48","author":"Satta","year":"2012","journal-title":"Blood Cells Mol Dis"},{"key":"10.1016\/j.hemonc.2016.02.003_b0130","first-page":"41","article-title":"Evaluation of signaling pathways involved in \u03b3-globin gene induction using fetal hemoglobin inducer drugs","volume":"7","author":"Rahim","year":"2013","journal-title":"Int J Hematol Oncol Stem Cell Res"},{"key":"10.1016\/j.hemonc.2016.02.003_b0135","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/S0009-8981(01)00672-6","article-title":"Diagnosis of hemoglobinopathies: electrophoresis vs HPLC","volume":"313","author":"Ou","year":"2001","journal-title":"Clin Chim Acta"},{"key":"10.1016\/j.hemonc.2016.02.003_b0140","first-page":"10","article-title":"Detection of abnormal hemoglobin variants by HPLC method: common problems with suggested solutions","volume":"2014","author":"Pant","year":"2014","journal-title":"Int Sch Res Notices"},{"key":"10.1016\/j.hemonc.2016.02.003_b0145","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1080\/10245330310001638983","article-title":"Clinico-haematological profile of HbE syndrome in adults and children","volume":"9","author":"Tyagi","year":"2004","journal-title":"Hematology"},{"key":"10.1016\/j.hemonc.2016.02.003_b0150","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1309\/AJCPP50JIXXZVLSS","article-title":"The range of hemoglobin A2 in hemoglobin E heterozygotes as determined by capillary electrophoresis","volume":"132","author":"Mais","year":"2009","journal-title":"Am J Clin Pathol"},{"key":"10.1016\/j.hemonc.2016.02.003_b0155","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.hemonc.2014.12.004","article-title":"Frequency of G\u03b3-globin promoter \u2212158 (C>T) XmnI polymorphism in patients with homozygous\/compound heterozygous beta thalassaemia","volume":"8","author":"Ali","year":"2015","journal-title":"Hematol Oncol Stem Cell Ther"},{"key":"10.1016\/j.hemonc.2016.02.003_b0160","doi-asserted-by":"crossref","first-page":"36","DOI":"10.59566\/IJBS.2012.8036","article-title":"Association between XmnI polymorphism and HbF level in sickle cell disease patients from Chhattisgarh","volume":"8","author":"Bhagat","year":"2012","journal-title":"Int J Biomed Sci"},{"key":"10.1016\/j.hemonc.2016.02.003_b0165","first-page":"17","article-title":"Molecular characterisation and frequency of G\u03b3Xmn I polymorphism in Chinese and Malay \u03b2-thalassaemia patients in Malaysia","volume":"28","author":"Wong","year":"2006","journal-title":"Malays J Pathol"},{"key":"10.1016\/j.hemonc.2016.02.003_b0170","unstructured":"Database of Single Nucleotide Polymorphisms (dbSNP). National Center for Biotechnology Information, National Library of Medicine. (dbSNP Build ID: {rs766432, rs11886868, rs9399137}). Available from: http:\/\/www.ncbi.nlm.nih.gov\/SNP\/2015. 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E\/\u03b2-thalassemia patients in Indonesia"],"short-title":[],"issued":{"date-parts":[[2016,4]]},"references-count":48,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2016]]}},"URL":"https:\/\/doi.org\/10.1016\/j.hemonc.2016.02.003","relation":{},"ISSN":["1658-3876"],"issn-type":[{"value":"1658-3876","type":"print"}],"subject":[],"published":{"date-parts":[[2016,4]]}}}