Vloga genov GLCCI1 IN SFXN1 pri zdravljenju otroške astme z glukokortikoidi

diplomsko delo univerzitetnega študijskega programa I. stopnje

Tjan Smrečnik (Author), Uroš Potočnik (Mentor), Vojko Berce (Co-mentor)

Abstract

Astma je najpogostejša kronična bolezen pri otrocih, ki prizadene dihala. Poznamo dva tipa astme, in sicer alergijsko in nealergijsko obliko astme. V svetu je možno zaznati strmo naraščanje obolevnosti za astmo po letu 1980. Številne študije so potrdile vpliv več kot stotih genov na razvoj in potek zdravljenja astme. Predvidevamo, da je vpliv posameznega gena izredno majhen. Velikokrat raziskave z nasprotujočimi si rezultati otežujejo določitev vloge, ki jo ima posamezni gen na razvoj in zdravljenje astme. Pri raziskovalnem delu smo analizirali genotip in izražanje genov za gena GLCCI1 in SFXN1 jih primerjali z različnimi kliničnimi parametri. Izražanje izbranih genov smo izmerili z metodo kvantitativnega PCR v realnem času. Gensko tipizacijo DNA polimorfizmov smo izvedli z metodo »Restriction Fragment Length Polymorphism« in »High Resolution Melt«. Z raziskavo smo želeli potrditi dosedanje rezultate raziskav za polimorfizem rs37972 za gen GLCCI1 in polimorfizem rs2644645 za gen SFXN1. Z raziskavo smo potrdili povečano tveganje za obolelost za astmo pri osebah, ki imajo za polimorfizem rs37972 genotip TT (p=0,010). Potrdimo lahko tudi vpliv genotipa CC, za polimorfizem rs37972, na vrednost parametra FEV1 (p=0,028). Za gen SFXN1 in polimorfizem rs2644645 lahko povežemo alel T s povečano količino eozinofilcev (p=0,013). Nadalje lahko potrdimo, da terapija s glukokortikoidi vpliva na izražanje gena SFXN1 (p=0,002). Rezultati, pridobljeni z raziskavo, bi lahko vplivali na razumevanje patogeneze astme in zdravljenju oz. lajšanju simptomov. Za zanesljivo uporabo genskih raziskav pri diagnosticiranju bolezni bodo v prihodnje potrebne še nadaljnje raziskave, ki bodo potrdile dosedanje povezave in analizirale gene ter njihove polimorfizme, ki imajo vpliv na razvoj in zdravljenje astme.

Keywords

otroška astma;farmakogenomika;GLCCI1;SFXN1;glukokortikoidi;

Data

Language:	Slovenian
Year of publishing:	2014
Typology:	2.11 - Undergraduate Thesis
Organization:	UM FKKT - Faculty of Chemistry and Chemical Engineering
Publisher:	[T. Smrečnik]
UDC:	575.616.248(043.2)
COBISS:	18227222
Views:	1698
Downloads:	73
Average score:	0 (0 votes)
Metadata:

Other data

Secondary language:	English
Secondary title:	THE ROLE OF GLCCI1 AND SFXN1 GENES IN THE GLUCOCORTICOID TREATMENT OF CHILDHOOD ASTHMA
Secondary abstract:	Asthma is the most common chronic disease among children that affects the respiratory system. There are two types of asthma, i.e. allergic and non-allergic asthma. Following 1980, it is possible to observe asthma incidence rates increasing steeply in the world. Numerous studies have confirmed the influence of more than a hundred genes on the development and the course of treatment of asthma. It is expected that the influence of an individual gene is extremely small. The research projects are often conflicting in their results and make it difficult to define the role of an individual gene on the development and the course of treatment of asthma. In our research work, we have analyzed the genotype and expression of the GLCCI1 and SFXN1 genes and compared them with various clinical parameters. The expression of chosen genes has been measured using quantitative real time PCR method. The genotyping of single nucleotide polymorphisms (SNPs) has been carried out by using »Restriction Fragment Length Polymorphism« and »High Resolution Melting curve« methods. In thos study we investigated for the role of SNP rs37972 in GLCCI1 gene and SNP rs2644645 in SFXN1 gene in the development and treatment of childhood asthma. We found increased risk for asthma in persons having TT genotype (p=0.0100) for rs37972 polymorphism. We also confirmed the influence of CC genotype on the FEV1 parameter value (p=0.0280) for rs37972 polymorphism. In relation to SFXN1 gene and rs2644645 polymorphism, T allele may be associated with the increased amount of eozinophyles (p=0.0130). Moreover, we identified the influence of glucocorticoids treatment on the expression of SFXN1 gene (p=0.0002). Our results contribute to understanding of asthma pathogenesis and asthma treatment with corticosteroids. Before using our results in clinical practice for further studies will be necessary in the future to confirm the associations identified in our study and to discover additional genes and their polymorphisms which influence the development and the course of treatment of asthma.
Secondary keywords:	childhood asthma;pharmacogenomics;GLCCI1;SFXN1;glucocorticoids;
URN:	URN:SI:UM:
Type (COBISS):	Bachelor thesis/paper
Thesis comment:	Univ. v Mariboru, Fak. za kemijo in kemijsko tehnologijo
Pages:	X, 40 str.
ID:	8730051