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Genotype frequencies of UDP-glucurnosyltransferase 1A1 gene polymorphism (UGT1A1) in the population of helathy Croatian pre-scholars

Introduction UGT1A1 genetic polymorphism with absent or very low UGT1A1 activity is associated with Gilbert’ s syndrome (GS) and other hyperbilirubinemias. The genetic basis of GS is the insertion of two additional TA nucleotides (resulting in seven repeats of TA) in the TATAA box, present in proximal promoter of UGT1A1 gene. As a result of the insertion UGT1A1*28 allele is formed. The aim of the study The aim of our study was to explore genotype frequencies of the UDP-glucuronosyltransferase 1A1 gene polymorphism in the TATAA box in the population of Croatian pre-scholars in order to define early risk for GS and other hyperbilirubinemias. We also investigated the association between different genotypes and plasma bilirubin concentration. Methods Study participants. The study included 323 pre-scholars with of median age 6&plusmn ; ; ; 0.5 (155 girls and 164 boys) who underwent routine medical examination for primary school registration at the division for school medicine in Pula General Hospital. Biochemical methods. Total plasma bilirubin concentration was determined by standard photometric method with diazo reagents on a Hitachi 717. Molecular methods. DNA extraction – salting-out method ; Polymerase chain reaction (PCR) ; Amplified fragments were resolved on Spreadex EL 500 gels using Elchrom Submerged Gel Electrophoresis Statistical methods. StatSoft, Inc. (1984-2005) STATISTICA (data analysis software system) version 7.1. Conclusions (1) The prevalence of genotype 7/7 in the population of Croatian pre-scholars is 9.8 % which correlates with the data of some similar Caucasians studies (2) Considering the fact that UGT1A1*28 is a frequently occurring mutation in population which affects drug metabolism, it would be important to introduce its genetic screening in routine diagnostics: a) it would help us to distinguish whether elevated bilirubin concentrations in some subjects are the result of UGT1A1 polymorphism or other disorder of liver metabolism b) it would enable more appropriate adjustment of dosage of therapeutic drugs which are metabolized through UGT1A1, in GS patients

Genotype; UGT1A1; polymorphism

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