title: Implication of genetic variation at the promoter and exon1 of UGT1A1 in occurrence of cholelithiasis in Tunisia.
abstract: Bilirubin is conjugated with glucoronic acid in the liver by UDP-glucuronosyltransferase 1A1 (UGT1A1). Polymorphisms at the promoter region or exon1 of UGT1A1 gene result in unconjugated hyperbilirubinemia and could be at the origin of gallstone formation. The purpose of this study is to determine whether polymorphisms in the promoter area and exon 1 of UGT1A1 can be considered as a risk factor for lithogenesis. Our study involved 76 patients with cholelithiasis as well as 141 unaffected subjects. For each subject an analysis of the bilirubin parameters was performed. We screened genetic variation in the promoter and exon1 UGT1A1 namely the A (TA) nTAA and the six following SNPs: 44T>G, 101C>A, 115C>G, 145C>T, 211G>A and 222 C>A by PCR/sequencing. Our findings show that subjects with (TA)(7) or (TA)(8) variant in their genotypes are associated with high bilirubin level. Furthermore, the comparison between patients and controls according to A(TA)nTAA variation demonstrated that (TA)(6)/(TA)(7) and (TA)(7)/(TA)(7) genotype and (TA)(7) and (TA)(8) alleles were significantly associated with an increased risk of gallstone diseases p=0.0017, p= 6.1 10(-6), p=1.5 10(-6) and p=0.025 respectively. However, polymorphisms in exon1 were normal in all studied subjects except for the 211G>A which appears to be associated with a protective effect p=7.910(-9); OR=0.03, CI95% (0.001-0.158).
authors.affiliation: Université de Tunis El Manar, Institut Pasteur de Tunis, Laboratoire d'hématologie moléculaire et cellulaire, Tunisie. Leila.chaouch@gmail.com
authors.forename: Leila
authors.initials: L
authors.lastname: Chaouch
authors.forename: Yossra
authors.initials: Y
authors.lastname: Said
authors.forename: Imen
authors.initials: I
authors.lastname: Moumni
authors.forename: Imen
authors.initials: I
authors.lastname: Mahjoubi
authors.forename: Arij Ben
authors.initials: AB
authors.lastname: Chaabene
authors.forename: Imen
authors.initials: I
authors.lastname: Darragi
authors.forename: Abderraouf
authors.initials: A
authors.lastname: Ghanem
authors.forename: Salem
authors.initials: S
authors.lastname: Abbes
mesh_terms: D000465:Algorithms; D000483:Alleles; D016022:Case-Control Studies; D002769:Cholelithiasis / Q000235:genetics*; D005091:Exons; D005260:Female; D014644:Genetic Variation / Q000235:genetics; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014416:Tunisia; D000099148:UGT1A1 Enzyme
chemical_list: D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme