engleski

UGT1A1 genetic variability and Gilbert syndome in Croatian pediatric population

Homozygous mutation in UGT1A1 gene - (TA)7 (allele 7) is associated to Gilbert syndrome (GS), compared to wild type (TA)6 (allele 6). Aim of our study was to estimate allelic and genotype frequencies in healthy children and children diagnosed as Gilbert syndrome. Association of mutant 7/7 genotype with elevated total serum bilirubin (TSB) concentration was also determined. 48 control subjects (mean age 15 years ; 63% females) and 48 patients (mean age 15 years ; 52% females) who were clinically diagnosed or suspected as Gilbert syndrome were included in the study. Associated diagnose was anorexia nervosa (AN) in 8 patients. For every subject TSB concentration was measured (umol/l) and UGT1A1 genotype was determined by PCR. Genotype distribution among controls was: 42% 6/6 (TSB 9.83 ; SD 5.60), 40% 6/7 (TSB 10.79 ; SD 6.05) and 19% 7/7 (TSB 20.39 ; SD 13.5). The allelic frequencies in this group for 6 and 7 alleles were 61% and 39% respectively. In GS group 6/6 genotype was not found, and 6/7 and 7/7 genotype distribution was 6% (TSB 25.73 ; SD 8.66) and 94% (TSB 41.88 ; SD 21.93) respectively. Allelic frequencies of 6 and 7 alleles were 3% and 97% respectively. There was no significant difference for genotype, allelic frequencies and TSB between males and females within groups. Genotype and allelic frequencies between GS and controls differed significantly: CHI(p)=0.001. TSB values among controls with 7/7 compared to 6/6 or 6/7 genotypes revealed significant difference: ANOVA(p)=0.001-0.011. TSB difference between 6/7 and 7/7 genotypes in GS group was not significant, what could be explained with small number of 6/7 genotypes. Among AN patients two were of 6/7 genotype while others were 7/7. Our preliminary results confirmed association of UGT1A1 7/7 genotype with Gilbert syndrome and elevated serum TSB values. Furthermore, it seems that there is some association between AN and clinical expression of GS. The future objective is to continue this investigation in order to estimate UGT1A1 frequencies in Croatian population on a larger number of subjects.

UGT1A1 gene; Gilbert syndrome; children

nije evidentirano