Vloga genov iz družine dejavnika tumorske nekroze pri nastanku in poteku multiple skleroze

diplomsko delo univerzitetnega študijskega programa I. stopnje

Martina Krušič (Avtor), Uroš Potočnik (Mentor), Tanja Hojs-Fabjan (Komentor), Katja Repnik (Komentor)

Povzetek

Multipla skleroza (MS) je kompleksna vnetna bolezen, ki prizadane osrednji živčni sistem. Bolniki so v povpečju stari med 20 in 40 let, za boleznijo pa pogosteje zbolevajo ženske. Točen vzrok nastanka sicer ni znan, vendar ga povezujemo z genetskimi dejavniki in vplivi iz okolja. K velikemu napredku v raziskovanju genetike MS so največ doprinesle asociacijske študije celotnega genoma (GWAS, ang. genome wide association studies), ki so do danes odkrile že več kot 100 lokusov, ki jih povezujemo z MS. Eden izmed znanih in pomembnih genetskih dejavnikov je tudi dejavnik tumorske nekroze. Pri pregledu objavljenih študij smo ugotovili močno statistično povezavo med SNP-ji rs1800693 (na genu TNFRSF1A), rs1077667 (na genu TNFSF14) in rs67297943 (na genu TNFAIP3) kot vzročnimi variantami, ki vplivajo na nastanek in potek MS. V okviru diplomske naloge smo omenjene SNP-je preiskovali na 180 slovenskih bolnikih obolelih z MS in 123 kontrolah. Za izbrane polimorfizme smo najprej načrtali začetne oligonukelotide, izvedli optimizacijo verižne reakcije s polimerazo (PCR) ter vzorce slovenskih bolnikov z MS in zdravih posameznikov genotipizirali z metodo analize talilne krivulje visoke ločljivosti (HRM). Rezultati za SNP rs1800693 so pokazali, da je frekvenca alela G povišana pri bolnikih z MS (0,489) v primerjavi z zdravimi kontrolami (0,418), razlika pa ni statistično signifikantna (p=0,069). Za SNP rs1077667, ki je lociran na genu TNFSF14, smo ugotovili povišano frekvenco alela A pri bolnikih z MS (0,279) v primerjavi z zdravimi posamezniki (0,215), za ta polimorfizem pa smo ugotovili tudi statistično značilne razlike v frekvenci genotipov glede na spol (p=0,042). Za SNP rs67297943 nismo odkrili statistično značilnih razlik med skupinami. Rezultati naše študije nakazujejo na vlogo genov iz družine dejavnika tumorske nekroze pri poteku in nastanku MS v slovenski populaciji.

Ključne besede

multipla skleroza;tumorska nekroza;genetika;polimorfizmi;diplomske naloge;

Podatki

Jezik:	Slovenski jezik
Leto izida:	2019
Tipologija:	2.11 - Diplomsko delo
Organizacija:	UM FKKT - Fakulteta za kemijo in kemijsko tehnologijo
Založnik:	[M. Krušič]
UDK:	575.1:616-004(043.2)
COBISS:	22665494
Št. ogledov:	842
Št. prenosov:	123
Ocena:	0 (0 glasov)
Metapodatki:

Ostali podatki

Sekundarni jezik:	Angleški jezik
Sekundarni naslov:	The role of tumor necrosis factor genes in prediction and progression of multiple sclerosis
Sekundarni povzetek:	Multiple sclerosis (MS) is a complex inflammatory disease that affects the central nervous system. Patients are between 20 and 40 years old and women are more likely to develop disease compared to men. Although the exact cause of the disease is unknown, we know that both genetic and environmental factors play role. Genome wide association studies (GWAS) brought great progress in genetics of MS, which to date have identified more than 100 locus associated with MS. One of the known and important genetic factors is also the tumour necrosis factor. After reviewing the published studies, we found a strong statistical association between SNPs rs1800693 (on TNFRSF1A gene), rs1077667 (on TNFSF14 gene), and rs67297943 (on TNFAIP3 gene) as causal variants affecting MS onset and course. Within the framework of the diploma thesis, we investigated these SNPs on 180 Slovenian patients with MS and 123 controls. We first designed primers for the selected polymorphisms and optimized primers using polymerase chain reaction (PCR). After optimization we genotyped samples of Slovenian MS patients and healthy individuals using the high resolution melting curve (HRM) method. Results for SNP rs1800693 showed that the frequency of G allele was higher in the patients with MS (0.489) compared to healthy controls (0.418). However, the difference was not statistically significant (p=0.069). For SNP rs1077667 located on the TNFSF14 gene, we found an increased frequency of allele A in the MS patients (0.279) compared to healthy individuals (0.215), and for this polymorphism we found statistically significant differences in genotype frequency by gender (p=0.042). For SNP rs67297943 we found no statistically significant differences between the groups. The results of our study suggest that tumour necrosis factor genes have a role in the course and onset of the MS in Slovenian population.
Sekundarne ključne besede:	multiple sclerosis;TNFRSF1A;TNFSF14;TNFAIP3;polymorphism;
Vrsta dela (COBISS):	Diplomsko delo/naloga
Komentar na gradivo:	Univ. v Mariboru, Fak. za kemijo in kemijsko tehnologijo
Strani:	VIII, 29 str.
ID:	11216654