UGT1A1 promoter polymorphisms and the development of hyperbilirubinemia and gallbladder disease in children with sickle cell anemia
Version of Record online: 6 AUG 2008
Copyright © 2008 Wiley-Liss, Inc.
American Journal of Hematology
Volume 83, Issue 10, pages 800–803, October 2008
How to Cite
Carpenter, S. L., Lieff, S., Howard, T. A., Eggleston, B. and Ware, R. E. (2008), UGT1A1 promoter polymorphisms and the development of hyperbilirubinemia and gallbladder disease in children with sickle cell anemia. Am. J. Hematol., 83: 800–803. doi: 10.1002/ajh.21264
- Issue online: 24 SEP 2008
- Version of Record online: 6 AUG 2008
- Accepted manuscript online: 6 AUG 2008 12:00AM EST
- Manuscript Accepted: 31 JUL 2008
- Manuscript Revised: 30 JUL 2008
- Manuscript Received: 26 NOV 2007
Genetic modifiers contribute to phenotypic variability in patients with sickle cell anemia (SCA). The influence of the bilirubin UDP-glucuronosyltransferase (UGT) 1A1 (TA)nTAA promoter polymorphism on bilirubin levels and gallbladder disease in SCA was examined using prospectively collected data from the Cooperative Study of Sickle Cell Disease. A total of 324 children with HbSS (median age 6.9 years) had UGT1A1 genotyping; 243 (75%) had common (TA)6 or (TA)7 alleles, whereas 81 (25.0%) had variant (TA)5 or (TA)8 alleles. The UGT1A1 genotype significantly influenced average bilirubin levels for the common alleles: 6/6 genotype = 2.36 ± 1.13 mg/dL, 6/7 genotype = 2.90 ± 1.54 mg/dL, and 7/7 genotype = 4.24 ± 2.11 mg/dL (P < 0.0001). Thirty-nine percent of children with the 7/7 genotype had documented gallbladder disease, compared with 18.2% with the 6/7 genotype and only 9.9% with the wildtype 6/6 UGT1A1 genotype (P = 0.001). To analyze the (TA)5 and (TA)8 variant alleles, three groups were generated, showing increasing bilirubin levels with increasing TA repeats and age. Group 3 (genotypes 6/8, 7/7, and 7/8) had a significantly greater rate of bilirubin change than Groups 1 (genotypes 5/6, 5/7, and 6/6) or 2 (genotype 6/7). These results validate previous smaller studies and confirm that the UGT1A1 promoter polymorphism exerts a powerful influence on bilirubin levels and the development of gallbladder disease in children with SCA. UGT1A1 genotyping should be considered as a screening tool for predicting children most likely to develop gallbladder disease at a young age. Am. J. Hematol., 2008. © 2008 Wiley-Liss, Inc.