title: UGT1A1 (TA)ngenotype is not the major risk factor of cholelithiasis in sickle cell disease children.
abstract: OBJECTIVE
  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)nrepeat 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)ngenotypes 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)npolymorphism 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.affiliation: Univ Lyon - University Claude Bernard Lyon 1 - EA 7424, Inter-university Laboratory of Human Movement Science, Villeurbanne, France.|Labex GR-Ex, Institut Universitaire de France, Paris, France.|Unité de Pathologie Moléculaire du Globule Rouge, Laboratoire de Biochimie et biologie moléculaire Grand Est, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Joly
authors.affiliation: Univ Lyon - University Claude Bernard Lyon 1 - EA 7424, Inter-university Laboratory of Human Movement Science, Villeurbanne, France.|Labex GR-Ex, Institut Universitaire de France, Paris, France.|Unité de Pathologie Moléculaire du Globule Rouge, Laboratoire de Biochimie et biologie moléculaire Grand Est, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Renoux
authors.affiliation: Unité de Pathologie Moléculaire du Globule Rouge, Laboratoire de Biochimie et biologie moléculaire Grand Est, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Lacan
authors.affiliation: Institut d'hématologie et d'oncologie pédiatrique - Hospices Civils de Lyon, Lyon, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Bertrand
authors.affiliation: Service de Médecine Interne, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Cannas
authors.affiliation: Institut d'hématologie et d'oncologie pédiatrique - Hospices Civils de Lyon, Lyon, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Garnier
authors.affiliation: Institut d'hématologie et d'oncologie pédiatrique - Hospices Civils de Lyon, Lyon, France.
authors.forename: Daniella
authors.initials: D
authors.lastname: Cuzzubbo
authors.affiliation: Institut d'hématologie et d'oncologie pédiatrique - Hospices Civils de Lyon, Lyon, France.
authors.forename: Kamila
authors.initials: K
authors.lastname: Kebaïli
authors.affiliation: Institut d'hématologie et d'oncologie pédiatrique - Hospices Civils de Lyon, Lyon, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Renard
authors.affiliation: Institut d'hématologie et d'oncologie pédiatrique - Hospices Civils de Lyon, Lyon, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Gauthier
authors.affiliation: Univ Lyon - University Claude Bernard Lyon 1 - EA 7424, Inter-university Laboratory of Human Movement Science, Villeurbanne, France.|Labex GR-Ex, Institut Universitaire de France, Paris, France.|Institut Universitaire de France, Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Pialoux
authors.affiliation: Univ Lyon - University Claude Bernard Lyon 1 - EA 7424, Inter-university Laboratory of Human Movement Science, Villeurbanne, France.|Labex GR-Ex, Institut Universitaire de France, Paris, France.
authors.forename: Cyril
authors.initials: C
authors.lastname: Martin
authors.affiliation: Labex GR-Ex, Institut Universitaire de France, Paris, France.|UMR Inserm 1134, Université des Antilles, CHU de Pointe à Pitre, Guadeloupe, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Romana
authors.affiliation: Univ Lyon - University Claude Bernard Lyon 1 - EA 7424, Inter-university Laboratory of Human Movement Science, Villeurbanne, France.|Labex GR-Ex, Institut Universitaire de France, Paris, France.|Institut Universitaire de France, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Connes
mesh_terms: D000293:Adolescent; D000483:Alleles; D000755:Anemia, Sickle Cell / Q000150:complications* / Q000235:genetics*; D015415:Biomarkers; D002648:Child; D002675:Child, Preschool; D002769:Cholelithiasis / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology*; D005260:Female; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D015994:Incidence; D007962:Leukocytes; D008297:Male; D012189:Retrospective Studies; D012307:Risk Factors; D055542:alpha-Globins / Q000235:genetics; D000099148:UGT1A1 Enzyme
chemical_list: D015415:Biomarkers; D014453:Glucuronosyltransferase; D055542:alpha-Globins; D000099148:UGT1A1 Enzyme
keywords: acute chest syndrome; cholelithiasis; hydroxyurea; reticulocytes; sickle cell disease children; vaso-occlusive crisis