{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T13:25:13Z","timestamp":1791033913277,"version":"4.1.0"},"reference-count":18,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2007,6,22]],"date-time":"2007-06-22T00:00:00Z","timestamp":1182470400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2007,7]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Serum bilirubin levels and predisposition to gallstones in sickle cell disease (SCD) are influenced by genetic variation in the hepatic uridine diphosphate (UDP)\u2010glucuronosyltransferase (<jats:italic>UGT1A1<\/jats:italic>) gene, but the association is not consistent. This study investigated whether variation in the gene encoding haem oxygenase (<jats:italic>HMOX1<\/jats:italic>), a rate\u2010limiting enzyme upstream of UGT1A in the haem catabolic pathway, and <jats:italic>\u03b1<\/jats:italic>\u2010thalassaemia could explain some of the inconsistent effects. The <jats:italic>UGT1A1<\/jats:italic> [TA]<jats:sub>n<\/jats:sub> and <jats:italic>HMOX1<\/jats:italic> [GT]<jats:sub>n<\/jats:sub> promoter polymorphisms and <jats:italic>\u03b1<\/jats:italic> globin genotypes were determined in 263 SCD patients (199 HbSS, 5 HbS\/<jats:italic>\u03b2<\/jats:italic><jats:sup>0<\/jats:sup>, 59 HbSC). Detection of gallstones was based on ultrasound of the liver\/biliary tree. Regression analysis showed that serum bilirubin levels and the incidence of gallstones were strongly associated with the number of <jats:italic>UGT1A1<\/jats:italic> [TA] repeats in all subjects (<jats:italic>P<\/jats:italic>\u2003&lt;\u20030\u00b70001 and <jats:italic>P<\/jats:italic>\u2003&lt;\u20030\u00b701, respectively). While <jats:italic>HMOX1<\/jats:italic> genotype had no effect, co\u2010inheritance of <jats:italic>\u03b1<\/jats:italic>\u2010thalassaemia reduced serum bilirubin levels in all SCD patients independently of the number of <jats:italic>UGT1A1<\/jats:italic> [TA] repeats. Each additional [TA] repeat is associated with an increase in mean serum bilirubin levels of 21% and cholelithiasis risk of 87% in SCD.<\/jats:p>","DOI":"10.1111\/j.1365-2141.2007.06643.x","type":"journal-article","created":{"date-parts":[[2007,6,23]],"date-time":"2007-06-23T02:28:14Z","timestamp":1182565694000},"page":"263-270","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":78,"title":["The linear effects of <i>\u03b1<\/i>\u2010thalassaemia, the <i>UGT1A1<\/i> and <i>HMOX1<\/i> polymorphisms on cholelithiasis in sickle cell disease"],"prefix":"10.1111","volume":"138","author":[{"given":"Nisha","family":"Vasavda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Menzel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheila","family":"Kondaveeti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Maytham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moji","family":"Awogbade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sybil","family":"Bannister","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliette","family":"Cunningham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Eichholz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne","family":"Daniel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iheanyi","family":"Okpala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony","family":"Fulford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swee 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