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

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.