title: Genetic link with cholelithiasis among pediatric SCA Tunisian patients: Examples of UGT1A1, SLCO1A2 and SLCO1B1.
abstract: OBJECTIVE
  Hyperbilirubinemia is often observed in chronic hemolysis and results in the formation of pigment cholelithiasis that could be increased by the presence of defected enzymes involved in the bilirubin metabolism. Indeed, this is the first report that interested in the study of polymorphisms in genes encoded for enzymes involved in the bilirubin metabolism: rs 4149056 of SLCO1B1 and rs4149000 of SLCO1A2 in combination with rs8175347 and rs887829 of UGT1A1 in order to find a correlation between the polymorphisms studied and the presence of gallstones in a population of sickle cell anemia (SCA) pediatric Tunisians.
  
  
  METHODS
  Our study involved 102 unrelated Tunisian subjects. All SCA patients are children (less than 16 years old) and were characterized by hyperbilirubinemia and 52 of them have cholelithiasis. The polymorphisms of the candidate genes were analyzed for all subjects by PCR/sequencing. Genotype and allele frequencies between cases and controls were compared using Pearson's chi-square test with a significance threshold of P < 0.05 (compare 2, version 1.02).
  
  
  RESULTS
  The novelty of this report is that children carrying the combined genotype of the rs studied: (TA7TA7)/TT/TC/GA have a higher risk to develop gallstones (P = 0.0027, RR = 18.27 (20.0061-915.28)).
  
  
  CONCLUSIONS
  Altogether our data provide the implication of UGT1A1 and SLCO1A2 in sickle cell anemia-related cholelithiasis.
authors.affiliation: a Université de Tunis El Manar, Institut Pasteur de Tunis, Laboratoire d'Hématologie Moléculaire et Cellulaire , Tunis , Tunisie.
authors.forename: Leila
authors.initials: L
authors.lastname: Chaouch
authors.affiliation: a Université de Tunis El Manar, Institut Pasteur de Tunis, Laboratoire d'Hématologie Moléculaire et Cellulaire , Tunis , Tunisie.
authors.forename: Miniar
authors.initials: M
authors.lastname: Kalai1
authors.affiliation: a Université de Tunis El Manar, Institut Pasteur de Tunis, Laboratoire d'Hématologie Moléculaire et Cellulaire , Tunis , Tunisie.
authors.forename: Imen
authors.initials: I
authors.lastname: Darragi
authors.affiliation: a Université de Tunis El Manar, Institut Pasteur de Tunis, Laboratoire d'Hématologie Moléculaire et Cellulaire , Tunis , Tunisie.
authors.forename: Imen
authors.initials: I
authors.lastname: Boudrigua
authors.affiliation: a Université de Tunis El Manar, Institut Pasteur de Tunis, Laboratoire d'Hématologie Moléculaire et Cellulaire , Tunis , Tunisie.
authors.forename: Dorra
authors.initials: D
authors.lastname: Chaouachi
authors.affiliation: a Université de Tunis El Manar, Institut Pasteur de Tunis, Laboratoire d'Hématologie Moléculaire et Cellulaire , Tunis , Tunisie.
authors.forename: Slim Ben
authors.initials: SB
authors.lastname: Ammar
authors.affiliation: a Université de Tunis El Manar, Institut Pasteur de Tunis, Laboratoire d'Hématologie Moléculaire et Cellulaire , Tunis , Tunisie.
authors.forename: F
authors.initials: F
authors.lastname: Mellouli
authors.affiliation: a Université de Tunis El Manar, Institut Pasteur de Tunis, Laboratoire d'Hématologie Moléculaire et Cellulaire , Tunis , Tunisie.
authors.forename: M
authors.initials: M
authors.lastname: Bjaoui
authors.affiliation: a Université de Tunis El Manar, Institut Pasteur de Tunis, Laboratoire d'Hématologie Moléculaire et Cellulaire , Tunis , Tunisie.
authors.forename: Salem
authors.initials: S
authors.lastname: Abbes
mesh_terms: D000293:Adolescent; D000755:Anemia, Sickle Cell / Q000150:complications / Q000235:genetics; D002648:Child; D002769:Cholelithiasis / Q000209:etiology / Q000235:genetics; D005260:Female; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D027381:Liver-Specific Organic Anion Transporter 1 / Q000235:genetics*; D008297:Male; D027361:Organic Anion Transporters / Q000235:genetics*; D012307:Risk Factors; D014416:Tunisia; D000099148:UGT1A1 Enzyme
chemical_list: D014453:Glucuronosyltransferase; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; D000099148:UGT1A1 Enzyme; C512988:SLCO1A2 protein, human; C503999:SLCO1B1 protein, human
keywords: Cholelithiasis; SLCO1A2; SLCO1B1; Sickle cell anemia; UGT1A1