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Blood, 1 February 2005, Vol. 105, No. 3, pp. 968-972. Prepublished online as a Blood First Edition Paper on September 23, 2004; DOI 10.1182/blood-2004-02-0521. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-02-0521v1 105/3/968    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Haverfield, E. V. Articles by Weatherall, D. J. Search for Related Content PubMed PubMed Citation Articles by Haverfield, E. V. Articles by Weatherall, D. J. Related Collections Red Cells Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS UGT1A1 variation and gallstone formation in sickle cell disease Eden V. Haverfield, Colin A. McKenzie, Terrence Forrester, Nourdine Bouzekri, Rosalind Harding, Graham Serjeant, Thomas Walker, Tim E. A. Peto, Ryk Ward, and David J. Weatherall From the Institute of Biological Anthropology and the Weatherall Institute of Molecular Medicine, University of Oxford, United Kingdom; the Tropical Medicine Research Institute, University of the West Indies, Mona, Kingston; and the Sickle Cell Trust, Kingston, Jamaica. Pigment gallstones are a common clinical complication of sickle cell (SS) disease. Genetic variation in the promoter of uridine diphosphate (UDP)–glucuronosyltransferase 1A1 (UGT1A1) underlies Gilbert syndrome, a chronic form of unconjugated hyperbilirubinemia, and appears to be a risk factor for gallstone formation. We investigated the association between UGT1A1 (TA)n genotype, hyperbilirubinemia, and gallstones in a sample of Jamaicans with SS disease. Subjects were from the Jamaican Sickle Cell Cohort Study (cohort sample, n = 209) and the Sickle Cell Clinic at the University of the West Indies, Kingston, Jamaica (clinic sample, n = 357). The UGT1A1 (TA)n promoter region was sequenced in 541 SS disease subjects and 111 healthy controls (control sample). Indirect bilirubin levels for (TA)7/(TA)7 and (TA)7/(TA)8 genotypes were elevated compared with (TA)6/(TA)6 (clinic sample, P < 10–5; cohort sample, P < 10–3). The (TA)7/(TA)7 genotype was also associated with symptomatic presentation and gallstones in the clinic sample (odds ratio [OR] = 11.3; P = 7.0 x 10–4) but not in the younger cohort sample. These unexpected findings indicate that the temporal evolution of symptomatic gallstones may involve factors other than the bilirubin level. Although further studies of the pathogenesis of gallstones in SS disease are required, the (TA)7/(TA)7 genotype may be a risk factor for symptomatic gallstones in older people with SS disease. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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