Naslov
UDP-glucuronosyl transferase (UGT1A1) TATA box polymorphism in pediatric population and Gilbert's syndrome

Autori
Žaja Franulović, Orjena

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Journal of Pediatric Gastroenterology and Nutrition - JPGN / - , 2009, 134-135

Skup
The 42th Annual meeting of The European Society of Paediatric Gastroenterology, Hepatolology and Nutrition- ESPGHAN

Mjesto i datum
Budimpešta, Mađarska, 03.06.2009. - 06.06.2009

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
UDP-GLUCORONYL TRANSFERASE, GILBERT SINDROME, PEDIATRIC

Sažetak
Background and Aim: Polymorphism of the promotor region of the UGT1A1 gene was shown to be associated with Gilbert syndrome (GS) in Caucasians. Insertion of additional TA nucleotide in TATA gene sequence, normally composed of 6 repeating TA dinucleotide sequences, causes a reduced gene expression and the reduction of UGT1A1 enzyme activity to 30% of normal values. The aim of the study was to determine eprevalence of (TA)n polymorphism of UGT1A1 gene and the genotype basis of Gilbert syndrome in Croatia, as well as to investigate the correlation between given genotypes and total serum bilirubin levels, in respect to the age and gender group. Methods: Blood samples were taken under the standardized conditions from 157 children (male/female: 75/82) aged 6 to 18 years (control group), and from 174 children clinically diagnosed with Gilbert syndrome (male/female: 98/76) aged 9 to 18 years. Total bilirubin were determined automatically by Olympus AU 600. TATA sequence of the UGT1A1 promotor was amplified by PCR, and the identification of the three possible genotypes, TA6/6, TA6/7 and TA7/7 was performed by electrophoresis on polyacrilamid gel using modified Sampietro’s method. Results: The correlation between total serum bilirubin levels (TB) and age was found in boys (r = 0.243 ; P = 0.035), but not in girls (r = 0.086 ; P = 0.442). In the group aged 6–12 years there was no gender difference in serum TB, while in the group aged 13–18 years TB was significantly higher in boys (15.9812.65mmol/L) than in girls (11.447.15mmol/L). TA6 allele frequency in control group is 0.649, and TA7 allele 0.351, with equal occurrence in both genders (P = 0.990). In control group, TA6/6 genotype was present in 44.0%, TA6/7 in 42.0%, and TA7/7 in 14.0% of children, without deviation from the theoretical frequencies (P = 0.792) and without any gender difference in distribution (P = 0.880). Trimodal distribution of serum bilirubin concentration was found wich depended on the genotype, with highest concentration in TA7/7 group. There was a statistically significant association of genotypes with serum TB (P<0.001)in all children as well as in gender groups. In GS patients TA7 allele frequency is 94.83% with symmetric distribution in both genders (P = 0.913). TA7/7 genotype was found in 90.80% of GS patients, TA6/7 in 8.05%, and TA6/6 in 1.15%, distributed equally in both genders in accordance with Hardy-Weinberg equilibrium (P = 0.409). Conclusions: Insertion of additional TA dinucleotide in the promotor region of UGT1A1 gene is the main cause of GS phenotype in the Croatian pediatric population.

Izvorni jezik
Engleski

POVEZANOST RADA