• Luis Méndez, Marcela Lagoa, Teresa Quiroga, Paula Margozzini, Lorena Azócar, Héctor R Molina, Alejandra Vera, Luis Villarroel, Marco Arrese, Jochen Hampe, Stephan Buch, and Juan F Miquel.
• Rev Med Chil. 2013 Oct 1; 141 (10): 126612741266-74.

BackgroundIn Europeans the TATA box TA7 repeat promoter variant in the UGT1A1 gene (UGT1A1*28) is the major determinant of bilirubin levels.AimTo study the prevalence of Gilbert Syndrome (GS) and its genetic determinants in Chile.Material And MethodsThree 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.ResultsPrevalence 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.ConclusionsWhile 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.

20 keywords...

hide…