UGT1A1 (TA)n genotype is not the major risk factor of cholelithiasis in sickle cell disease children.

Abstract

OBJECTIVES:

Because of the increased hemolytic rate, a significant proportion of patients with sickle cell disease (SCD) are prone to develop cholelithiasis. The present study investigated the role of several genetic factors (UGT1A1 promoter (TA)n repeat polymorphism, alpha-globin status), hematological parameters, clinical severity, and hydroxyurea (HU) therapy on the occurrence of cholelithiasis in SCD.

METHODS:

One hundred and fifty-eight children (2-18 yr old) regularly followed at the University Hospital of Lyon (France) were included. A multivariate Cox model was used to test the associations between cholelithiasis and the different parameters analyzed.

RESULTS:

We confirmed that alpha-thalassemia and low basal reticulocyte (RET) count were independent protective factors for cholelithiasis while 7/7, 8/8 and 7/8 UGT1A1 (TA)n genotypes were independent predisposing factors for this complication. We also showed for the first time that HU treatment decreased the risk for cholelithiasis while frequent vaso-occlusive crises and acute chest syndrome events increased that risk.

CONCLUSIONS:

Our findings demonstrate that UGT1A1 (TA)n polymorphism is not the only factor triggering gallstone formation in SCD. Cholelithiasis is also modulated by RET count, the number of deleted alpha-genes, HU therapy and the frequency of vaso-occlusive events.

• Authors: Philippe Joly, Céline Renoux, Philippe Lacan, Yves Bertrand, Giovanna Cannas, Nathalie Garnier, Daniella Cuzzubbo, Kamila Kebaïli, Cécile Renard, Alexandra Gauthier, Vincent Pialoux, Cyril Martin, Marc Romana, Philippe Connes
• Journal: European journal of haematology (Eur J Haematol) Vol. 98 Issue 3 Pg. 296-301 (Mar 2017) ISSN: 1600-0609 [Electronic] England
• PMID: 27981643 (Publication Type: Journal Article)
• Copyright: © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemical References

• Biomarkers
• alpha-Globins
• UGT1A1 enzyme
• Glucuronosyltransferase

Topics

• Adolescent
• Alleles
• Anemia, Sickle Cell (complications, genetics)
• Biomarkers
• Child
• Child, Preschool
• Cholelithiasis (diagnosis, epidemiology, etiology)
• Female
• Genotype
• Glucuronosyltransferase (genetics)
• Humans
• Incidence
• Leukocytes
• Male
• Retrospective Studies
• Risk Factors
• alpha-Globins (genetics)