{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T06:29:05Z","timestamp":1770704945407,"version":"3.49.0"},"reference-count":53,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2007,9,25]],"date-time":"2007-09-25T00:00:00Z","timestamp":1190678400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2007,12]]},"abstract":"<jats:p>We evaluated the contribution of 67 single nucleotide polymorphisms (SNPs) within the \u03b2\u2010globin gene cluster to disease severity in groups of 207 mild\u2010 and 305 severe unrelated patients from Thailand with Hemoglobin E (HbE)\/\u03b2<jats:sup>0<\/jats:sup>\u2010thalassemia and normal \u03b1\u2010globin genes. Our analysis showed that these SNPs comprise two distinct linkage disequilibrium blocks, one containing the \u03b2\u2010globin gene and the other extending from the locus control region (LCR) to the \u03b4 gene, which are separated by a recombination hotspot in the narrow region of the \u03b2\u2010globin gene promoter. Forty\u2010five SNPs within the interval including the LCR region and the \u03b4 gene showed strong association with disease severity. The strongest association was observed with the <jats:italic>Xmn<\/jats:italic>I polymorphism located 158\u2010bp upstream to the G\u03b3 gene (p\u2003=\u20034.6E\u221212). Carriers of the T allele of <jats:italic>Xmn<\/jats:italic>I were more likely to have a milder disease course and higher level of fetal hemoglobin (HbF) in both the mild (p\u2003=\u20030.005) and severe (p\u2003=\u20038.7E\u221206) patient groups. Haplotype analysis revealed that the T allele of <jats:italic>Xmn<\/jats:italic>I was nearly always in <jats:italic>cis<\/jats:italic> with the HbE allele. The high frequency of this haplotype may be favored by positive selection against malarial infection. Further studies are needed to validate this hypothesis and determine whether <jats:italic>Xmn<\/jats:italic>I or another closely linked variant modulates severity and HbF levels in patients with \u03b2<jats:sup>0<\/jats:sup>\u2010thalassemia\/HbE disease.<\/jats:p>","DOI":"10.1111\/j.1399-0004.2007.00897.x","type":"journal-article","created":{"date-parts":[[2010,7,19]],"date-time":"2010-07-19T12:01:32Z","timestamp":1279540892000},"page":"497-505","source":"Crossref","is-referenced-by-count":27,"title":["\u03b2\u2010Globin gene cluster polymorphisms are strongly associated with severity of HbE\/\u03b2<sup>0<\/sup>\u2010thalassemia"],"prefix":"10.1111","volume":"72","author":[{"given":"Q","family":"Ma","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"Abel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"O","family":"Sripichai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Whitacre","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V","family":"Angkachatchai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W","family":"Makarasara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P","family":"Winichagoon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Fucharoen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Braun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"LA","family":"Farrer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2007,9,25]]},"reference":[{"key":"e_1_2_6_2_2","first-page":"369","article-title":"The 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