BACKGROUND/AIMS: Gilbert's syndrome is a benign form of a deficiency in bilirubin glucuronidation. It is associated with a homozygous polymorphism, A(TA)7TAA instead of A(TA)6TAA, in the TATA-box of the promoter region of the bilirubin UDP-glucuronyltransferase gene. In this study the correlation between this promoter region polymorphism and in vitro human liver bilirubin UDP-glucuronyltransferase enzyme activity was investigated. METHODS: Liver samples from organ transplant donors n=39) and two known Gilbert's syndrome patients were used for measuring bilirubin UDP-glucuronyltransferase enzyme activity and for isolation of DNA followed by detection of the promoter region polymorphism by polymerase chain reaction. Genotypes were assigned as follows; 6/6: homozygous for the A(TA)6TAA-allele, 7/7: homozygous for the A(TA)7TAA-allele, and 6/7: heterozygous with one of each alleles. RESULTS: Seventeen out of 39 subjects (44%) had the homozygous 6/6 genotype, 18 subjects (46%) had the heterozygous 6/7 genotype, whereas four individuals (10%) and the two individuals with Gilbert's syndrome had the 7/7 genotype correlated with Gilbert's syndrome. This resulted in an allele frequency of 0.33 for the A(TA)7TAA-allele. The median bilirubin UDP-glucuronyltransferase enzyme activity of the 17 subjects with the 6/6 genotype (1565 nmol/g liver/h) was significantly higher than the activity of the 18 subjects with the 6/7 genotype (985 nmol/g liver/h; p<0.05) and the six individuals with the 7/7 genotype (749 nmol/g liver/h; p<0.005). No significant differences in enzyme activity were found between the 6/7 and the 7/7 genotype groups. CONCLUSIONS: The results indicate a close association between the promoter region genotype and the expression of hepatic bilirubin UDP-glucuronyltransferase enzyme activity. Subjects who have a 7/7 genotype have the lowest enzyme activity, whereas subjects with the heterozygous 6/7 genotype have an intermediate enzyme activity.
BACKGROUND/AIMS: Gilbert's syndrome is a benign form of a deficiency in bilirubin glucuronidation. It is associated with a homozygous polymorphism, A(TA)7TAA instead of A(TA)6TAA, in the TATA-box of the promoter region of the bilirubin UDP-glucuronyltransferase gene. In this study the correlation between this promoter region polymorphism and in vitro human liver bilirubin UDP-glucuronyltransferase enzyme activity was investigated. METHODS: Liver samples from organ transplant donors n=39) and two known Gilbert's syndromepatients were used for measuring bilirubin UDP-glucuronyltransferase enzyme activity and for isolation of DNA followed by detection of the promoter region polymorphism by polymerase chain reaction. Genotypes were assigned as follows; 6/6: homozygous for the A(TA)6TAA-allele, 7/7: homozygous for the A(TA)7TAA-allele, and 6/7: heterozygous with one of each alleles. RESULTS: Seventeen out of 39 subjects (44%) had the homozygous 6/6 genotype, 18 subjects (46%) had the heterozygous 6/7 genotype, whereas four individuals (10%) and the two individuals with Gilbert's syndrome had the 7/7 genotype correlated with Gilbert's syndrome. This resulted in an allele frequency of 0.33 for the A(TA)7TAA-allele. The median bilirubin UDP-glucuronyltransferase enzyme activity of the 17 subjects with the 6/6 genotype (1565 nmol/g liver/h) was significantly higher than the activity of the 18 subjects with the 6/7 genotype (985 nmol/g liver/h; p<0.05) and the six individuals with the 7/7 genotype (749 nmol/g liver/h; p<0.005). No significant differences in enzyme activity were found between the 6/7 and the 7/7 genotype groups. CONCLUSIONS: The results indicate a close association between the promoter region genotype and the expression of hepatic bilirubin UDP-glucuronyltransferase enzyme activity. Subjects who have a 7/7 genotype have the lowest enzyme activity, whereas subjects with the heterozygous 6/7 genotype have an intermediate enzyme activity.
Authors: Thomas Hofmann; Stefanie Klenow; Anke Borowicki; Chris I R Gill; Beatrice L Pool-Zobel; Michael Glei Journal: Genes Nutr Date: 2010-02-09 Impact factor: 5.523
Authors: Edward P Acosta; Michelle A Kendall; John G Gerber; Beverly Alston-Smith; Susan L Koletar; Andrew R Zolopa; Sangeeta Agarwala; Michael Child; Richard Bertz; Lara Hosey; David W Haas Journal: Antimicrob Agents Chemother Date: 2007-06-18 Impact factor: 5.191
Authors: S D Zucker; X Qin; S D Rouster; F Yu; R M Green; P Keshavan; J Feinberg; K E Sherman Journal: Proc Natl Acad Sci U S A Date: 2001-10-16 Impact factor: 11.205
Authors: C-F Xu; B H Reck; Z Xue; L Huang; K L Baker; M Chen; E P Chen; H E Ellens; V E Mooser; L R Cardon; C F Spraggs; L Pandite Journal: Br J Cancer Date: 2010-04-13 Impact factor: 7.640