Variations of the bilirubin uridine-diphosyphoglucuronosyl transferase 1A1 gene in healthy Taiwanese

The activity of uridine-diphosphoglucuronosyl transferase 1 (UGT1) may influence the concentration of serum bilirubin. Because UGT1 is too labile to be measured with classical biochemical methods, we analysed the whole UGT1A1 gene in 290 healthy Taiwanese adults by using the polymerase chain reaction method, and investigated the relationship between UGT1A1 genotypes and serum bilirubin levels. The results showed that slightly more than 50% of the subjects had one or more variant sites in UGT1A1 gene, The most common variant was A(TA)(6)TAA/A(TA)(7)TAA (6/7) in the promoter area, followed by heterozygous variation within the coding region, compound heterozygous and homozygous variations, Among the four variant sites within the coding region, 211 G to A was the predominate one, 1091 C to T was a novel variation, and 686 C to A was associated with 6/7, Subjects with 6/7 or heterozygous variation within the coding region or compound heterozygous (plus one homozygous) variation had significantly higher bilirubin levels than those with wild UGT1A1 gene, When the 290 subjects were stratified into six groups according to their serum bilirubin concentrations, the bilirubin levels were correlated well to the frequencies of variant UGT1A1 gene. Our results show that there is a strong association between UGT1A1 gene and bilirubin levels in healthy Taiwanese adults. The occurrence of A(TA)(7)TAA allele was relatively rare and the variation rate within the coding region was much higher in Taiwanese compared to that in Caucasians. Pharmacogenetics 10:539-544 (C) 2000 Lippincott Williams & Wilkins.