Haplotypes in the UGT1A1 gene and their role as genetic determinants of bilirubin concentration in healthy German volunteers

Clin Biochem. 2009 Nov;42(16-17):1635-41. doi: 10.1016/j.clinbiochem.2009.08.011. Epub 2009 Sep 2.

Abstract

Background: Genetic variations of UDP-glucuronyltransferase 1A1 (UGT1A1) influence the concentration of serum bilirubin. We investigated the association of four common polymorphisms including UGT1A1-53(TA)(n), and common haplotypes of the UGT1A1 gene with bilirubin levels in 218 Caucasian volunteers.

Methods: Total bilirubin was measured in serum of 218 healthy Caucasian volunteers. Genotyping of four genetic variants was performed: UGT1A1-53(TA)(6/7), UGT1A1c.-3279T>G, UGT1A1c.-3156G>A, and UGT1A1c.211G>A. The association between polymorphisms/haplotypes and bilirubin levels were determined.

Results: Minor allele frequencies were 0.36 for UGT1A1-53(TA)(7), 0.47 for c.-3279G, 0.33 for c.-3156A and 0.006 for c.211A. The three promoter polymorphisms were in close linkage disequilibrium. Common haplotypes were: -53(TA)(6)/c.-3279T/c.211G (frequency 0.530), -53(TA)(7)/c.-3279G/c.211G (frequency 0.365), and -53(TA)(6)/c.-3279G/c.211G (frequency 0.099). Male sex, UGT1A1-53(TA)(6/7) and the c.-3279GG variant were significantly associated with higher bilirubin concentrations.

Conclusions: Two UGT1A1 promoter polymorphisms (-53(TA)(6/7) and c.-3279T>G) and a common haplotype of the UGT1A1 gene are associated with serum bilirubin concentrations in Caucasians.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Base Sequence
  • Bilirubin / blood*
  • DNA Primers
  • Female
  • Gene Frequency
  • Germany
  • Glucuronosyltransferase / genetics*
  • Haplotypes*
  • Humans
  • Linkage Disequilibrium
  • Male
  • Polymorphism, Genetic
  • Promoter Regions, Genetic
  • White People

Substances

  • DNA Primers
  • UGT1A1 enzyme
  • Glucuronosyltransferase
  • Bilirubin