title: [Prevalence of Gilbert syndrome and its genetic determinants in Chile].
abstract: BACKGROUND
  In Europeans the TATA box TA7 repeat promoter variant in the UGT1A1 gene (UGT1A1*28) is the major determinant of bilirubin levels.
  
  
  OBJECTIVE
  To study the prevalence of Gilbert Syndrome (GS) and its genetic determinants in Chile.
  
  
  METHODS
  Three different studies were conducted. The prevalence of GS in Chile was assessed in 991 subjects with normal liver tests (ALT and GGT) from the 2nd National Health Survey. We defined GS as a total bilirubin (TB) between 1.4-5mg/dL. The second study assessed the genotype prevalence of SNP rs6742078 (in LD with UGT1A1*28) and rs4149056 in 500 DNA samples of non-related Hispanics. Finally, a case-control study was designed to assess the phenotype-genotype correlation. UGT1A1*28 and rs4149056 variants were determined by direct sequencing and allelic discrimination assays (TaqMan), respectively.
  
  
  RESULTS
  Prevalence of GS in the general Chilean population was 2.6% (4.5% in males and 0.5% in female). No correlation with age, educational level or home location was found. Genotypes for UGT1A1*28 (TA6/6 50.5%, TA6/7 37.8%, TA7/7 11.7%) and rs4149056 (TT 74.1%, CT 22.8%, and CC 3.1%) variants were similar to Europeans. In the case-control study, most patients with GS were homozygotes for UGT1A1*28 (TA7/7, 74%). Of note, 44% of patients with intermediate TB levels were also TA7/7, compared to 7% in normal subjects. SLCO1B1 genotype was not correlated with TB levels.
  
  
  CONCLUSIONS
  While the prevalence of GS was lower in Chile compared to Europeans (~5%), the prevalence of UGT1A1*28 homozygotes was similar (~12%). In Chilean Hispanics, the UGT1A1*28 variant explain 75% of GS phenotype.
authors: Luis
authors: L
authors: Méndez
authors: Marcela
authors: M
authors: Lagoa
authors: Teresa
authors: T
authors: Quiroga
authors: Paula
authors: P
authors: Margozzini
authors: Lorena
authors: L
authors: Azócar
authors: Héctor R
authors: HR
authors: Molina
authors: Alejandra
authors: A
authors: Vera
authors: Luis
authors: L
authors: Villarroel
authors: Marco
authors: M
authors: Arrese
authors: Jochen
authors: J
authors: Hampe
authors: Stephan
authors: S
authors: Buch
authors: Juan F
authors: JF
authors: Miquel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001663:Bilirubin / Q000235:genetics*; D001800:Blood Specimen Collection; D016022:Case-Control Studies; D002677:Chile / Q000453:epidemiology; D005260:Female; D059647:Gene-Environment Interaction; D056726:Genetic Association Studies; D005878:Gilbert Disease / Q000453:epidemiology* / Q000235:genetics; D014453:Glucuronosyltransferase; D006801:Humans; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D044465:White People / Q000235:genetics; D000099148:UGT1A1 Enzyme
chemical_list: D001663:Bilirubin; D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme