engleski

Rare variants in TATA box of UDP glucuronosyltranferase gene in Croatian population

Background. Gilbert’ s syndrome is a chronic or recurrent mild benign hyperbilirubinemia caused by decreased activity of the UDP glucuronosyltranferase. The most common cause of Gilbert’ s syndrome in Caucasian population is homozygous variant of A(TA)7TAA promoter polymorphism. Alleles with different number of (TA) repeats are also described in literature, but their frequency in Caucasian population is low. In this study we report frequencies of different polymorphisms in promoter TATA box in Croatian population. Methods. 1109 subjects with suspected Gilbert’ s syndrome were included in this study. Genotyping of (TA)6 and (TA)7 alleles was performed using high resolution electrophoretic separation of amplified PCR products on Spreadex EL300 gels (Elchrom Scientific). In 7 subjects aberrant electrophoretic patterns were observed and additionally sequenced on ABI Prism 310 Genetic Analyzer (Applied Biosystems). Results. Out of 1109 subjects, 1102 could be identified as having either (TA)6 or (TA)7 alleles. Genotype distributions were as follows: 53.91%, 26.24% and 18.87% for the (TA)7/(TA)7, (TA)6/(TA)7 and (TA)6/(TA)6, respectively. 7 samples displayed patterns that couldn’ t be identified as one of these alleles and were sequenced to identify polymorphic variants in the PCR amplified TATA box. Results showed presence of rare alleles (TA)5 and (TA)8 which are also associated with Gilbert’ s phenotype. 4 subjects had (TA)5/(TA)7, two had (TA)7/(TA)8 and one had (TA)6/(TA)8 genotype. Conclusion. Frequencies of different TA repeats in TATA box of UDP glucuronosyltranferase gene found in our study correspond well to those described in literature, with (TA)5 and (TA)8 alleles being very rare in Caucasian population.

hyperbilirubinemia; Gilbert’ s syndrome; genetic polymorphism; neonatal jaundice

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