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Polimorfizmi gena uključenih u inflamatorne, antioksidativne i imunoregulatorne procese kod obolelih od bronhijalne astme

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Author
Despotović, Milena R.
Mentor
Jevtović Stoimenov, Tatjana
Committee members
Pavlović, Dušica
Stanković, Ivana
Bašić, Jelena
Mitrović, Tatjana
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Abstract
Bronchial asthma (BA) is a chronic, inflammatory disease of the airways that is caused by the influence of genetic and environmental factors. Genes involved in inflammation, oxidative stress and immunomodulation might be important factors in BA pathogenesis. The aim of the PhD thesis was to examine the association of single nucleotide polymorphisms (SNPs) of tumor necrosis factor-α (TNF-α, rs1800629), antioxidative enzymes, catalase (CAT, rs7943316) and manganese superoxide dismutase (MnSOD, rs4880), and vitamin D receptor (VDR, rs2228570 and rs1544410) in BA, as well as their mutual influence on BA onset. Furthermore, the risk for BA development in the presence of minor alleles and heterozygous and homozygous genotypes containing minor allele was determined. The influence of VDR gene SNPs on 25(OH)D3 blood levels was determined, as well. Total of 79 patients with BA and 95 healthy controls were involved in this study. SNPs were determines using PCR-RFLP method, while 25(OH)D3 concentr...ation was measured using HPLC method. Mutual influence of studied SNPs was determined using MDR software. Obtained results show that Val allele of rs4880 SNP (p=0.001) and genotypes containing Val allele (p=0.001) have significantly higher prevalence in BA patients compared to healthy controls. Carriers of AlaVal and ValVal genotypes have 2.7- and 5.9- fold respectively higher risk for BA development compared to the carriers of AlaAla genotype. Val allele is associated with 2.2-fold higher risk for BA compared to Ala allele. Genotype FF (p=0.004) and F allele (p=0.001) of the rs2228570 are significantly higher in healthy controls compared to patients with BA. Moreover, fb haplotype (p=0.009) and FfBb diplotype (p=0.018) have significantly higher prevalence in patients compared to controls. Carriers of FF genotype and F allele have 5.3-fold and 2.3-fold lower risk for asthma development compared to the carriers of ff genotype and f allele of rs2228570 SNP. Moreover, carriers of Fb and FB haplotypes have 2-fold lower risk for BA compared to the carriers of fb haplotype. 25(OH)D3 levels are not significantly different between patients with BA and healthy subjects, as well as between the carriers of the certain genotypes of rs2228570 and rs7943316 (p>0.05). Mutual interaction for the model with 3 SNPs (rs7943316, rs4880, rs1544410) shows that rs1544410 has positive (synergistic) interaction effect with rs1544410, while negative (redundant) interaction effect is obtained between rs1544410 and rs4880, as well as between rs4880 and rs794336. Mutual interaction for the model with 5 SNPs (rs1800629, rs7943316, rs4880, rs2228570, rs1544410) shows redundant effect of rs2228570 with all other SNPs. In conclusion, rs4880 of MnSOD gene and rs2228570 of VDR gene are associated with BA. Presence of rs4880 Val allele is associated with BA and increased risk for disease development. Allele F of rs2228570 SNP has protective effect on BA development and it is associated with the lower risk of asthma development.

Faculty:
Универзитет у Нишу, Медицински факултет
Date:
10-05-2016
Projects:
  • Preventive, therapeutic, and ethical approach in preclinical and clinical studies of the genes and modulators of redox cell signaling in immune, inflammatory and proliferative cell response (RS-41018)
Keywords:
bronhijalna astma / bronchial asthma / polimorfizmi jednog nukleotida / TNF-α / katalaza / MnSOD / receptor vitamina D / single nucleotide polymorphism / TNF-α / catalase / MnSOD / vitamin D receptor
[ Google Scholar ]
Handle
https://hdl.handle.net/21.15107/rcub_nardus_7213
URI
https://nardus.mpn.gov.rs/handle/123456789/7213
http://eteze.ni.ac.rs/application/showtheses?thesesId=4340
https://fedorani.ni.ac.rs/fedora/get/o:1183/bdef:Content/download
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