Variations at the six
nucleotides -3279 (T > G), -53 (A[TA]6 TAA > A[TA]7 TAA), 211 (G > A), 686 (C > A), 1091 (C > T), and 1456 (T > G) in the
UDP-glucuronosyltransferase 1A1 (UGT1A1) gene were determined in 178 Taiwanese patients with
Gilbert's syndrome and in 200 healthy adults. Every subject was classified as a genotype depending on variation status of the six
nucleotides in the UGT1A1 gene. The UGT1A1 activity for each genotype was calculated and then those genotypes were divided into 10 subgroups (Q1~Q10) according to their UGT1A1 activities, by using 10% as an interval. There were 24 genotypes observed, with UGT1A1 activity ranged 9%~100% of normal. There were two and six subjects with
Gilbert's syndrome and none of healthy controls carrying genotypes in the Q1 and Q2 subgroups, respectively. The odds of developing
Gilbert's syndrome were significantly higher for subjects carrying genotypes in the Q3, Q4, and Q5 subgroups than for those with genotype in the Q10 subgroup (odds ratios: 240.22, 59.80, and 14.67, respectively, P < .001 for each). Among the 178 patients of
Gilbert's syndrome, serum
bilirubin value was inversely correlated with UGT1A1 activity (r = -.306, P < .001). The sensitivity was 72.0% and the specificity was 90.5% by using UGT1A1 activity ≦40% of normal as the cut-off point to distinguish between healthy subjects and patients of
Gilbert's syndrome. Our results demonstrate that UGT1A1 activity is certainly a determinate for serum
bilirubin value and UGT1A1 activity ≦40% of normal is a proper risk factor for the development of
Gilbert's syndrome.