Polimorfizam gena GRIK1 u ovisnika o alkoholu

master's thesis

• Title (english): Polymorphism of GRIK1 u ovisnika o alkoholu
• Author: Hrvoje Bekina
• Mentor: Dubravka Švob Štrac (mentor)
• Mentor: Domagoj Đikić (mentor)
• Committee member: Domagoj Đikić (predsjednik povjerenstva)
• Committee member: Petar Kružić (član povjerenstva)
• Committee member: Zlatko Liber (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2014-11-04, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Glutamat, glavni ekscitacijski neurotransmitor u mozgu, ima značajnu ulogu u posredovanju učinaka alkohola i razvoju alkoholizma. Od svih glutamatnih receptora, kainatni receptori kao i njihova uloga u alkoholizmu, do sada su najmanje istraženi. Jedan od gena za glutamatne receptore za koji se utvrdila povezanost s alkoholizmom je gen GRIK1 koji kodira za podjedinicu GluR5 kainatnih receptora. Iako istraživanja pokazuju da pojedini polimorfizmi u genu GRIK1 značajno utječu na djelovanje topiramata, lijeka učinkovitog u liječenju alkoholizma, potrebne su daljnje studije. Cilj istraživanja bio je istražiti postoji li povezanost polimorfizma rs2186305 u genu GRIK1 i alkoholizma u ispitanika hrvatskog podrijetla. Učestalost pojedinih genotipova i alela gena GRIK1 uspoređena je između alkoholičara i zdravih ispitanika, različitog spola i pušačkog statusa. Istražila se je i raspodjela genotipova i alela polimorfizma rs2186305 u skupinama alkoholičara podijeljenih s obzirom na dob početka zlouporabe alkohola, suicidalno i agresivno ponašanje, kao i na tip alkoholizma prema Cloningeru. Haplotipska analiza polimorfizma rs2186305 u kombinaciji s polimorfizmom rs2832407 napravljena je u zdravih osoba, kao i u osoba ovisnih o alkoholu. Dobiveni rezultati trebali bi pridonijeti boljem razumijevanju uloge gena koji kodira za podjedinicu GluR5 glutamatnih kainatnih receptora u razvoju alkoholizma, te doprinijeti istraživanjima novih potencijalnih ciljeva u liječenju ove kronične bolesti.

Abstract (english)

Glutamate, the major excitatory neurotransmitter in the brain, has an important role in mediating the effects of alcohol and the development of alcoholism. Among different glutamate receptors, kainate receptors and their role in alcoholism are so far the least explored. One of the genes for glutamate receptors that has been found to be associated with alcoholism is GRIK1 gene, encoding the GluR5 subunit of kainate receptors. Although research shows that certain polymorphisms in the GRIK1 gene significantly affect the activity of topiramate, a drug effective in the treatment of alcoholism, further studies are needed. The aim of the research is to investigate the association between rs2186305 polymorphism of GRIK1 gene and alcoholism in subjects of Croatian origin. The frequency of GRIK1 genotypes and alleles was compared between alcoholics and healthy subjects, divided according to gender and smoking status. Moreover, the distribution of genotypes and allele of polymorphism rs2186305 has been investigated in group of alcoholics subdivided according to age of onset of alcohol abuse, suicidal and aggressive behavior, as well as the type of alcoholism according to Cloninger classification. Haplotype analysis of the polymorphism rs2186305 in combination with polymorphism rs2832407 has been conducted in healthy individuals, as well as in subjects addicted to alcohol. The results should contribute to a better understanding of the role of the GRIK1 gene, encoding subunit GluR5 kainate glutamate receptors, in the development of alcoholism, as well as to the research of new potential targets for the therapy of this chronic disease.

• Keywords: gen GRIK1; kainatni receptor; polimorfizam; rs2186305; ovisnost o alkoholu
• Keywords (english): GRIK1 gene; kainate receptor; polymorphism; rs2186305; alcohol dependence
• Language: croatian
• URN:NBN: urn:nbn:hr:217:751639
• Study programme: Title: Experimental Biology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra eksperimentalne biologije (magistar/magistra eksperimentalne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Access restricted to students and staff of home institution
• Created on: 2017-04-25 13:03:01