20.500.12556/DKUM-66587 Polimorfizmi v genih FAAH in ABHD4, vključenih v biološko pot endokanabinoidov anandaminov, pri bolnikih z otroško astmo Polymorphisms in genes FAAH and ABHD4 involved in a biological pathway of endocannbinoids anandamin in childhood asthma patients V diplomskem delu smo analizirali povezave med izbranima polimorfizmoma posameznega nukleotida (SNP-ji) in bolniki z astmo, in sicer polimorfizem rs1384962, ki je v bližini gena ABHD4 ter rs3863641, ki je v bližini gena FAAH. Oba gena sta vključena v biološko pot endokanabinoidov anandaminov.. Preučevali smo vpliv polimorfizmov na klinične in laboratorijske parametre pri astmatikih, ki so prejemali terapijo s kortikosteroidi (CS) in antileukotrieni (AL). Analizo smo naredili na slovenskih otrocih z astmo in zdravih posameznikih. Izbrane SNP-je smo genotipizirali z metodo talilne krivulje visoke ločljivosti (HRM). Naša študija je pokazala, da imajo bolniki z alelom G polimorfizma rs1384962 statistično značilno boljši odziv na terapijo s CS in AL kot bolniki z alelom A (p = 0.0017). Pri analizi polimorfizma rs3863641 pa smo ugotovili, da imajo boljši odziv bolniki z alelom A kot pa bolniki z alelom G (p = 0.0009). Nismo pa našli značilne razlike v frekvencah posameznih alelov in genotipov v polimorfizmu rs1384962 in rs3863641 med skupinami astmatikov, atopijskih astmatikov, neatopijskih astmatikov ter kontrolno skupino. V prihodnosti bi bilo zanimivo omenjena polimorfizma še podrobneje preučiti, da bi na ta način lahko uporabljali endokanabinoidni sistem kot tarčo za zdravljenje astme in da bi zdravljenje lahko prilagodili posamezniku glede na njegov genetski zapis. This graduation thesis presents a study of genotypes and allele connections with polymorphism rs1384962 of ABHD4 gene and rs3863641 of gene FAAH, which are connected with asthma and the endocannabinoid system. We studied the impact of the individual genotypes and alleles of these polymorphisms within clinical and laboratory parameters in asthmatic patients receiving CS and AL therapy. Neither polymorphism rs1384962 nor rs3863641 reveal any statistically significant differences in the frequencies of individual alleles and genotypes between groups of asthmatics, atopic asthmatics, nonatopic asthmatics and the control group. Our study showed that patients with the G allele polymorphism rs1384962 had a significantly better response to CS and AL therapy, than patients with allele A. In the case of polymorphism rs3863641, we found that the treatment was more effective in patients with A allele than in patients with allele G. In the future, it would be interesting to analyze those two polymorphisms in more depth so that we could use the endocannabinoid system as a target for the treatment of asthma, and adapt treatment to individuals depending on their genetic code. Astma Endokanabinoidi Anandamin FAAH ABHD4 Asthma Endocanabinoids Anandamin FAAH ABHD4 true true false [D. Kresnik] Slovenski jezik Angleški jezik Diplomsko delo/naloga 2017-07-03 17:46:38 2017-07-24 11:55:47 2022-08-01 12:56:44 2019-07-11 15:52:23 2017 0 Maribor 0 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616.248:544.344.015.4(043.2) 20687638 URN:SI:UM:DK:YSLUAZNL UN_Kresnik_Davor_2017.pdf UN_Kresnik_Davor_2017.pdf 1 7F1FA61D437B3F00CE6DAF76A0C06260 c60948f65fe418c5f81a73c7a6f8113fa7be3d52ff29761c60ad825b7fef6654 70f71f14-7c0e-11eb-bb7a-00155d0001ca 20.500.12556/dkum/03278b00-e349-4fe1-9d19-9b62409aa5d8 https://dk.um.si/Dokument.php?lang=slv&id=114460 Fakulteta za kemijo in kemijsko tehnologijo 0 0 0