Farmakogenetika – individualizirani način liječenja genetičkih poremećaja

undergraduate thesis

• Title (english): Pharmacogenetics – individualized treatment of genetic disorders
• Author: Mirna Biluš
• Mentor: Mirjana Pavlica (mentor)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2011, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Farmakogenetika je grana znanosti koja proučava povezanost genotipa sa različitom reakcijom na terapiju nekim lijekovima. Potencijal farmakogenetike je velik jer će dobiveni rezultati istraživanja omogućiti i olakšati individualizirano liječenje. Tiopurin S-metiltransferaza (TPMT) je enzim koji inaktivira tiopurinske lijekove te sprječava njihov prelazak u toksične produkte. U genu za TPMT postoje polimorfizmi koji uzrokuju varijabilnu aktivnost enzima. Kod pacijenata koji su deficijentni za TPMT može doći do trovanja krvi i kod njih se doza tiopurinskih lijekova mora smanjiti. Četiri varijante polimorfnih alela za TPMT su najviše proučavane jer imaju najveći utjecaj na smanjenje aktivnosti TPMT-a: TPMT*2, TPMT*3A, TPMT*3B i TPMT*3C te čine 95% nasljedne deficijencije za enzim TPMT. Varfarin je oralni antikoagulans koji u stanici djeluje kao inhibitor vitamin K epoksid reduktaza kompleksa (podjedinice VKORC1). Varijabilni farmakogenetički odgovor ovisi o polimorfizmima dva enzima: CYP2C9 (enzim koji metabolizira lijek) i VKORC1. Najčešći varijantni aleli za CYPC9 su CYP2C9*2 i CYP2C9*3. Osoba koja ima te alele za najbolji učinak mora primati manju dozu lijeka. Varijante kompleksa VKORC1 se mogu podijeliti u 4 haplotipa: VKORC1*1, *2, *3 i *4. VKORC1*1 se uzima kao referenca, za haplotip VKORC1*2 potrebna je manja doza lijeka, a haplotipovi VKORC1*3 i VKORC1*4 trebaju veću dozu varfarina Serotoninski transporter (SERT) omogućuje ponovni ulazak serotonina u neurone. Gen za SERT sadrži polimorfizme koji utječu na njegovu ekspresiju i funkciju. SERT je cilj djelovanja nekih antidepresiva. Dosadašnja istraživanja su pokazala da zbog polimorfizama u promotorskoj regiji gena za SERT može doći do slabijeg reagiranja na terapiju antidepresivima, ali zbog postojanja kontradiktornih rezultata trenutno nije moguće na temelju genotipa odrediti optimalnu dozu lijeka.

Abstract (english)

Pharmacogenetics is a branch of science that studies the association of genotype with individual response to drug therapy. The potential of pharmacogenetics is great because further research will enable and facilitate individualized treatment of some diseases. Tiopurin S-methyltransferase (TPMT) is an enzyme that inactivates thiopurine drugs and prevents their transformation to toxic products. The TPMT gene exhibits genetic polymorphisms that cause variable enzyme activity. TPMT deficient patients are at high risk of hematologic toxicity and should be treated with reduced dose of thiopurine drugs. Four polymorphic variant TPMT alleles have been most studied because they have the greatest impact on reducing activity of TPMT: TPMT*2, TPMT*3A, TPMT*3B and TPMT*3C. Warfarin, an anticoagulant, acts as an antagonist of vitamin K epoxide reductase complex (VKORC1 subunit). Polymorphisms in CYP2C9 (metabolizes Warfarin) and VKORC1 cause variable patient response. The most common variant alleles for CYPC9 are CYP2C9*2 and CYP2C9*3. Patients with these alleles require a lower dose of drug. VKORC1 variants can be divided into four haplotypes: VKORC1 *1, *2, *3 and *4. VKORC1*1 is considered the reference, while patients with the VKORC1*2 require lower and patients with VKORC1*3 and VKORC1*4 higher warfarin doses. Serotonin transporter (SERT) is the transporter protein in charge of serotonin reuptake. SERT gene polymorphisms affect its expression and function. SERT is the target of some antidepressants. Some studies have shown that polymorphisms in the SERT gene promotor region cause poor response to antidepressants, but because of some conflicting results it is not possible yet to determine the optimal antidepressant dose based on genotype.

• Keywords: farmakogenetika
• Keywords (english): pharmacogenetics
• Language: croatian
• URN:NBN: urn:nbn:hr:217:543982
• Study programme: Title: Molecular Biology; Study programme type: university; Study level: undergraduate; Academic / professional title: sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) molekularne biologije (sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) molekularne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2018-04-05 08:05:16