Rare TA repeats in promoter TATA box of the UDP glucuronosyltranferase (UGT1A1) gene in Croatian subjects.
BACKGROUND
Gilbert's syndrome is a chronic or recurrent mild unconjugated hyperbilirubinemia caused by decreased activity of UDP glucuronosyltranferase (UGT1A1). The most common cause of Gilbert's syndrome in Caucasians is homozygous variant of the A(TA)7TAA promoter polymorphism. Alleles with five or eight TA repeats have also been described, but they are very rare in Caucasian populations.


METHODS
Over a 6-year period (2001-2006), 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. In seven subjects, aberrant electrophoretic patterns were observed and additionally sequenced on an ABI Prism 310 Genetic Analyzer.


RESULTS
Genotype distributions for 1102 subjects with (TA)6 or (TA)7 alleles were as follows: 54.10%, 26.33% and 18.94% for the (TA)7/(TA)7, (TA)6/(TA)7 and (TA)6/(TA)6, respectively. Sequencing of seven samples that could not be identified as one of these alleles identified four subjects with the (TA)5/(TA)7, two with the (TA)7/(TA)8 and one with the (TA)6/(TA)8 genotype.


CONCLUSIONS
Genotyping of TA repeats in the promoter region of the UGT1A1 gene revealed the presence of rare alleles with five or eight TA repeats, with a very high frequency of the (TA)7 allele in subjects suspected of having Gilbert's syndrome.
Nikolac
Nora
N
University Department of Chemistry, Sestre Milosrdnice University Hospital, Zagreb, Croatia. nora.nikolac@gmail.com
Simundic
Ana-Maria
AM
Topic
Elizabeta
E
Jurcic
Zvonko
Z
Stefanovic
Mario
M
Dumic
Jerka
J
Goreta
Sandra Supraha
SS
D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002648:Child; D015331:Cohort Studies; D017523:Croatia; D017931:DNA Primers; D005260:Female; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D008297:Male; D011401:Promoter Regions, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D012189:Retrospective Studies; D016385:TATA Box
D017931:DNA Primers; D014453:Glucuronosyltransferase