Molekularna dijagnostika Gilbertova sindroma

master's thesis

• Title (english): Molecular diagnosis of Gilbert's syndrome
• Author: Ana Karaga
• Mentor: Jadranka Sertić (mentor)
• Committee member: Iveta Šimić (predsjednik povjerenstva)
• Committee member: Jasna Lovrić (član povjerenstva)
• Committee member: Jadranka Sertić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Medical Chemistry, Biochemistry and Clinical Chemistry); Zagreb
• Defense date and country: 2015-07-15, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Medical Biochemistry

Abstract

Gilbertov sindrom je autosomno-recesivna bolest karakterizirana povećanim vrijednostima nekonjugiranog bilirubina i predstavlja najčešći nasljedni uzrok povišenog bilirubina. Hiperbilirubinemija ovog sindroma je uzrokovana reduciranom aktivnošću enzima glukuronil transferaze koja konjugira bilirubin čineći ga topljivim u vodi. Prevalencija Gilbertovog sindroma je 4-16%. Kliničke se manifestacije uobičajeno javljaju tijekom puberteta kada koncentracija steroidnih hormona povisuje vrijednost bilirubina u krvi. Gilbertov sindrom je češći u muškaraca nego u žena (2-7:1). Klinička slika je karakterizirana intermitentnim epizodama blage žutice koja može biti izazvana dehidracijom, stresom, infekcijama ili gladovanjem. Ostali simptomi su nespecifični i rijetki. Oni uključuju proljev, mučninu, umor i gubitak apetita. Gilbertov sindrom je benigna bolest koja ne zahtijeva specifično liječenje. Važno je upozoriti pacijenta na lijekove koji mogu povisiti vrijednosti bilirubina u krvi i uzrokovati žuticu. Postoje lijekovi koji se metaboliziraju putem enzima glukuronil transferaze, te zbog reducirane aktivnosti enzima, imajutoksičan učinak na tijelo.
Cilj ovog istraživanja je bio utvrditi frekvenciju umetanja TA dinukleotida u promotorsku regiju UGT1A1 gena. Pacijenti s Gilbertovim sindromom imaju 7 TA ponavljanja na oba alelaregije UGT1A1 gena (TA7/TA7) dok su zdravi pojedinci homozigoti za TA6 alel (TA6/TA6). Heterozigoti imaju i 6 i 7 TA ponavljanja (TA6/TA7) i u većini slučajeva ne razvijaju hiperbilirubinemiju.
Analiza 1091 krvnih uzoraka je otkrila da su 136 ili 12% ispitanika zdravi pojedinci koji imaju TA6/TA6 genotip, 254 ili 24% su heterozigoti (TA6/TA7) i 701 ili 64% ispitanika su pacijenti sa 7 TA ponavljanja na oba alela (TA7/TA7). Zaključak: Gilbertov sindrom je benigna bolest koja ne zahtijeva specifično liječenje. Važno je upozoriti oboljele osobe na provocirajuće čimbenike koji dovode do žutice te na lijekove koji mogu dovesti do hiperbilirubinemije.

Abstract (english)

Gilbert's syndrome is an autosomal-recessive disease characterized by elevated levels of unconjugated bilirubin. This disease is the most common hereditary cause of increased bilirubin. Hyperbilirubinemia in this syndrome, is caused by the reduced activity of enzyme glucuronyltransferase which conjugates bilirubin making it soluble in water. The prevalence of Gilbert's syndrome is 4-16%. Clinical manifestations usually occur during puberty when the concentration of steroid hormones increases the level of bilirubin in the bloodstream. This syndrome is more common in men than in women (2-7:1). Gilbert's syndrome is characterized by intermittent episodes of mild jaundice that may be caused by dehydration, stress, infections and starvation. Other symptoms are nonspecific and rare. They include diarrhea, nausea, fatigue and loss of appetite. Gilbert's syndrome is a benign disease that doesn't requires specific treatment. It is important to warn patients about medicines that may increase the serum concentration of bilirubin in the bloodstream and cause jaundice. There are also some medicines that are metabolized through enzyme glucuronyltransferase and, because of its reduced level, can have toxic effects on the body. The aim of this study was to review the frequency insertion of the TA dinucleotide in gene region UGT1A1. Patients with Gilbert's syndrome have 7 TA repeats on both alleles in UGT1A1gene region (TA7/TA7) while healthy individuals are homozygotes for TA6 alel (TA6/TA6) . Heterozygotes have both 6 and 7 TA repeats (TA6/TA7) and in most cases they will not have hyperbilirubinemia. The analysis of 1091 blood samples revealed that 136 or 12% respondents are healthy individuals with TA6/TA6 genotype, 254 or 24% are heterozygotes (TA6/TA7) and 701 or 64% are patients with 7 TA repeats on both alleles (TA7/TA7). Conclusion: Gilbert's syndrome is a benign disease that doesn't require specific treatment. It is important to warn patients on provocative factores that can lead to jaundice and also on medications that can cause hyperbilirubinemia.

• Keywords: Gilbertov sindrom; TA dinukleotid; UGT1A1
• Keywords (english): Gilbert's syndrome; TA dinucleotide; UGT1A1
• Language: croatian
• URN:NBN: urn:nbn:hr:105:902725
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2016-08-16 09:37:57