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

Abstract

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)6TAA/A(TA)7TAA (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)7TAA allele was relatively rare and the variation rate within the coding region was much higher in Taiwanese compared to that in Caucasians.

Intra-ethnic differences in genetic variants of the UGT-glucuronosyltransferase 1A1 gene in Chinese populations

“…[16][17][18] In the present study, the (TA)7 allele was significantly associated with higher T-Bil concentrations, in line with previous reports. 15,19 However, different to Koreans, no association between 211A allele and bilirubin level was found. Carriers of the haplotypes 4 (À3279G; À3156A; (TA)7; 211G; 686C) had increased serum T-Bil concentrations compared with the other groups.…”

“…10 Association between increased serum T-Bil levels and genetic variants of UGT1A1 was reported in healthy Koreans and Taiwanese. 14,15 A significant correlation between SN-38 and bilirubin glucuronidation has been found, high serum T-Bil concentration seemed to be a reasonably good predictor of lower irinotecan clean rate. [16][17][18] In the present study, the (TA)7 allele was significantly associated with higher T-Bil concentrations, in line with previous reports.…”

Comprehensive UGT1A1 Genotyping in a Japanese Population by Pyrosequencing

“…The most common nonsynonymous single-nucleotide polymorphism (SNP) (211GϾA) that causes an amino acid alteration (glycine to arginine at codon 71) is found in Asian populations at frequencies of 13-23% (7,8 ). The 686CϾA (P229Q) variation in the Taiwanese has a frequency of 2.8% (8 ).…”

Gly71Arg UGT1A1 polymorphism is associated with breast cancer susceptibility in Han Chinese women

“…The UGT1A1*6 polymorphism, causing a G→A substitution in the first exon, is a common SNP in the Asian population, but is rare in the Caucasian and African populations (Huang et al, 2000). Our study demonstrated the potential association of the UGT1A1*6 SNP with the development of breast cancer in a Chinese population for the first time.…”