TY  - JOUR
AU  - Stefanović, Milan
AU  - Stojković, Ljiljana
AU  - Životić, Ivan
AU  - Dinčić, Evica
AU  - Stanković, Aleksandra
AU  - Živković, Maja
PY  - 2024
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12715
AB  - Multiple sclerosis (MS), a noncurable autoimmune neurodegenerative disease, requires constant research that could improve understanding of both environmental and genetic factors that lead to its occurrence and/or progression. Recognition of the genetic basis of MS further leads to an investigation of the regulatory role of genetic variants on gene expression. Among risk variants for MS, Ikaros zinc finger 3 (IKZF3) gene variant rs12946510 was identified as one of the top-ranked and the expression quantitative trait loci (eQTL) for genes residing in chromosomal locus 17q12- 21. The study aimed to investigate the association of gene expression of the immunologically relevant genes, which map to indicated locus, ORMDL3, GSDMB, and IKZF3, with MS and rs12946510 genotype, taking into account disease phase, clinical parameters of disease progression, and severity and immunomodulatory therapy. We used TaqMan® technology for both allelic discrimination and gene expression determination in 67 relapsing MS patients and 50 healthy controls. Decreased ORMDL3 and GSDMB mRNA levels had significant associations with MS and rs12946510 TT rare homozygote among patients. Significant positive correlations between ORMDL3 and GSDMB mRNA expression were observed in both patients and controls. We detected the significant between-effect of sex and rs12946510 on the expression of ORMDL3 in the patient group and interferon β therapy and rs12946510 on GSDMB expression. Our results show the association of ORMDL3 and GSDMB mRNA expression with the clinical manifestation of MS and confirm that IKZF3 rs12946510 exerts the eQTL effect on both genes in multiple sclerosis. Besides providing novel insight related to MS phases and interferon β therapy, the study results confirm previous studies on regulatory genetic variants, autoimmunity, and MS.
T2  - Heliyon
T1  - Expression levels of GSDMB and ORMDL3 are associated with relapsing-remitting multiple sclerosis and IKZF3 rs12946510 variant
VL  - 10
IS  - 3
SP  - e25033
DO  - 10.1016/j.heliyon.2024.e25033
ER  - 

@article{
author = "Stefanović, Milan and Stojković, Ljiljana and Životić, Ivan and Dinčić, Evica and Stanković, Aleksandra and Živković, Maja",
year = "2024",
abstract = "Multiple sclerosis (MS), a noncurable autoimmune neurodegenerative disease, requires constant research that could improve understanding of both environmental and genetic factors that lead to its occurrence and/or progression. Recognition of the genetic basis of MS further leads to an investigation of the regulatory role of genetic variants on gene expression. Among risk variants for MS, Ikaros zinc finger 3 (IKZF3) gene variant rs12946510 was identified as one of the top-ranked and the expression quantitative trait loci (eQTL) for genes residing in chromosomal locus 17q12- 21. The study aimed to investigate the association of gene expression of the immunologically relevant genes, which map to indicated locus, ORMDL3, GSDMB, and IKZF3, with MS and rs12946510 genotype, taking into account disease phase, clinical parameters of disease progression, and severity and immunomodulatory therapy. We used TaqMan® technology for both allelic discrimination and gene expression determination in 67 relapsing MS patients and 50 healthy controls. Decreased ORMDL3 and GSDMB mRNA levels had significant associations with MS and rs12946510 TT rare homozygote among patients. Significant positive correlations between ORMDL3 and GSDMB mRNA expression were observed in both patients and controls. We detected the significant between-effect of sex and rs12946510 on the expression of ORMDL3 in the patient group and interferon β therapy and rs12946510 on GSDMB expression. Our results show the association of ORMDL3 and GSDMB mRNA expression with the clinical manifestation of MS and confirm that IKZF3 rs12946510 exerts the eQTL effect on both genes in multiple sclerosis. Besides providing novel insight related to MS phases and interferon β therapy, the study results confirm previous studies on regulatory genetic variants, autoimmunity, and MS.",
journal = "Heliyon",
title = "Expression levels of GSDMB and ORMDL3 are associated with relapsing-remitting multiple sclerosis and IKZF3 rs12946510 variant",
volume = "10",
number = "3",
pages = "e25033",
doi = "10.1016/j.heliyon.2024.e25033"
}

Stefanović, M., Stojković, L., Životić, I., Dinčić, E., Stanković, A.,& Živković, M.. (2024). Expression levels of GSDMB and ORMDL3 are associated with relapsing-remitting multiple sclerosis and IKZF3 rs12946510 variant. in Heliyon, 10(3), e25033.
https://doi.org/10.1016/j.heliyon.2024.e25033

Stefanović M, Stojković L, Životić I, Dinčić E, Stanković A, Živković M. Expression levels of GSDMB and ORMDL3 are associated with relapsing-remitting multiple sclerosis and IKZF3 rs12946510 variant. in Heliyon. 2024;10(3):e25033.
doi:10.1016/j.heliyon.2024.e25033 .

Stefanović, Milan, Stojković, Ljiljana, Životić, Ivan, Dinčić, Evica, Stanković, Aleksandra, Živković, Maja, "Expression levels of GSDMB and ORMDL3 are associated with relapsing-remitting multiple sclerosis and IKZF3 rs12946510 variant" in Heliyon, 10, no. 3 (2024):e25033,
https://doi.org/10.1016/j.heliyon.2024.e25033 . .

TY  - CONF
AU  - Stojković, Ljiljana
AU  - Stefanović, Milan
AU  - Dinčić, Evica
AU  - Mačak, Nataša
AU  - Seke, Mariana
AU  - Živković, Maja
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12712
AB  - Introduction: The hallmark pathogenic mechanisms of multiple sclerosis (MS) are proposed to be associated with long chain polyunsaturated fatty acids(LC-PUFA)-mediated neuroinflammation, through LC-PUFA-derived pro- and anti-inflammatory eicosanoids. Variants in genes coding for fatty acid desaturases (FADS), the key enzymes in LC-PUFA biosynthesis from essential fatty acids, are associated with changesin circulating LC-PUFA levels. The aim of thisstudy wasto investigate the FADS2 intronic variants, rs174576 (C/A), rs174593 (T/C) and rs174616 (G/A), in association with MS. Methods: The study involved 124 patients with relapsing-remitting form of MS and 83 healthy control subjects. The FADS2 gene variants were detected using TaqMan® SNP genotyping assays. Analysis of allele and genotype distributions in patients and controls was done by using the chi-square test. Results: According to the model of dominant effect of allele, genotypes containing the alternative, C, allele of FADS2 rs174593 variant were significantly less frequent in MS patients than in controls (MS: TT=57,26%, TC+CC=42,74%; controls: TT=42,17%, TC+CC=57,83%; p=0,03). In addition, the frequency of rs174593 C allele was significantly lower in patients, compared to controls (MS: T=0,76, C=0,24; controls: T=0,67, C=0,33; p=0,04). The frequency distributions of rs174576 and rs174616 alleles and genotypes were not significantly different between the study groups (p>0,05). Conclusion: The obtained resultssupply a rationale for further investigation of the association of FADS2 rs174593 with circulating LC-PUFA levels, in the context of MS. The genotype-LC-PUFA phenotype association could provide guidelinesfor personalized LC-PUFA supplementation, to potentially ameliorate the disease course and improve the effectiveness of therapy
C3  - CoMBoS2 – the Second Congress of Molecular Biologists of Serbia : Book of abstracts
T1  - FADS2 gene variant rs174593 is associated with multiple sclerosis
SP  - 88
EP  - 88
UR  - https://hdl.handle.net/21.15107/rcub_vinar_12712
ER  - 

@conference{
author = "Stojković, Ljiljana and Stefanović, Milan and Dinčić, Evica and Mačak, Nataša and Seke, Mariana and Živković, Maja",
year = "2023",
abstract = "Introduction: The hallmark pathogenic mechanisms of multiple sclerosis (MS) are proposed to be associated with long chain polyunsaturated fatty acids(LC-PUFA)-mediated neuroinflammation, through LC-PUFA-derived pro- and anti-inflammatory eicosanoids. Variants in genes coding for fatty acid desaturases (FADS), the key enzymes in LC-PUFA biosynthesis from essential fatty acids, are associated with changesin circulating LC-PUFA levels. The aim of thisstudy wasto investigate the FADS2 intronic variants, rs174576 (C/A), rs174593 (T/C) and rs174616 (G/A), in association with MS. Methods: The study involved 124 patients with relapsing-remitting form of MS and 83 healthy control subjects. The FADS2 gene variants were detected using TaqMan® SNP genotyping assays. Analysis of allele and genotype distributions in patients and controls was done by using the chi-square test. Results: According to the model of dominant effect of allele, genotypes containing the alternative, C, allele of FADS2 rs174593 variant were significantly less frequent in MS patients than in controls (MS: TT=57,26%, TC+CC=42,74%; controls: TT=42,17%, TC+CC=57,83%; p=0,03). In addition, the frequency of rs174593 C allele was significantly lower in patients, compared to controls (MS: T=0,76, C=0,24; controls: T=0,67, C=0,33; p=0,04). The frequency distributions of rs174576 and rs174616 alleles and genotypes were not significantly different between the study groups (p>0,05). Conclusion: The obtained resultssupply a rationale for further investigation of the association of FADS2 rs174593 with circulating LC-PUFA levels, in the context of MS. The genotype-LC-PUFA phenotype association could provide guidelinesfor personalized LC-PUFA supplementation, to potentially ameliorate the disease course and improve the effectiveness of therapy",
journal = "CoMBoS2 – the Second Congress of Molecular Biologists of Serbia : Book of abstracts",
title = "FADS2 gene variant rs174593 is associated with multiple sclerosis",
pages = "88-88",
url = "https://hdl.handle.net/21.15107/rcub_vinar_12712"
}

Stojković, L., Stefanović, M., Dinčić, E., Mačak, N., Seke, M.,& Živković, M.. (2023). FADS2 gene variant rs174593 is associated with multiple sclerosis. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia : Book of abstracts, 88-88.
https://hdl.handle.net/21.15107/rcub_vinar_12712

Stojković L, Stefanović M, Dinčić E, Mačak N, Seke M, Živković M. FADS2 gene variant rs174593 is associated with multiple sclerosis. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia : Book of abstracts. 2023;:88-88.
https://hdl.handle.net/21.15107/rcub_vinar_12712 .

Stojković, Ljiljana, Stefanović, Milan, Dinčić, Evica, Mačak, Nataša, Seke, Mariana, Živković, Maja, "FADS2 gene variant rs174593 is associated with multiple sclerosis" in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia : Book of abstracts (2023):88-88,
https://hdl.handle.net/21.15107/rcub_vinar_12712 .

TY  - JOUR
AU  - Kolić, Ivana
AU  - Stojković, Ljiljana S.
AU  - Stanković, Aleksandra
AU  - Stefanović, Milan
AU  - Dinčić, Evica
AU  - Živković, Maja
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9542
AB  - Background: Leptin (LEP), leptin receptor (LEPR) and peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC1A) are involved in the pathogenesis of multiple sclerosis (MS) by affecting the inflammatory response and reactive oxygen species production. LEP rs7799039 and LEPR rs1137101 genetic variants modify the serum LEP levels and PGC1A rs8192678 alters the PGC1A activity. The study objective was to explore the associations of these variants with susceptibility to MS, disease course/clinical parameters and also with peripheral blood mononuclear cell expression of the target genes and plasma LEP concentrations, in the study subjects. Methods: The study groups included 528 patients with MS and 429 controls. TaqMan® assays were used for genotyping and gene expression quantification. The Chi-square, parametric and nonparametric tests and simple/multiple logistic regression were performed for the statistical analysis of data. Results: A multiple logistic regression model including all three investigated variants, applied to patients (RRMS + SPMS) and controls, showed that PGC1A rs8192678 minor allele had an increased risk for the occurrence of disease, with OR (95%CI) = 1,32 (1,01–1,73), P = 0,04. Between-effect of gender and LEPR variant on the multiple sclerosis severity score (MSSS) was identified (P = 0,005). In male patients (relapsing-remitting and secondary progressive), LEPR minor allele carriers had increased MSSS (GG + AG vs AA, median (minimum–maximum) = 5,38 (0,64–9,88) vs 4,27 (0,78–9,63); P = 0,01, Padj = 0,03). In relapsing-remitting patients LEP rs7799039 affected the LEP gene expression (P = 0,006; Padj = 0,04). Conclusion: The current findings implicate an impact of investigated genetic variants on the pathogenesis of MS. © 2021 Elsevier B.V.
T2  - Gene
T1  - Association study of rs7799039, rs1137101 and rs8192678 gene variants with disease susceptibility/severity and corresponding LEP, LEPR and PGC1A gene expression in multiple sclerosis
VL  - 774
SP  - 145422
DO  - 10.1016/j.gene.2021.145422
ER  - 

@article{
author = "Kolić, Ivana and Stojković, Ljiljana S. and Stanković, Aleksandra and Stefanović, Milan and Dinčić, Evica and Živković, Maja",
year = "2021",
abstract = "Background: Leptin (LEP), leptin receptor (LEPR) and peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC1A) are involved in the pathogenesis of multiple sclerosis (MS) by affecting the inflammatory response and reactive oxygen species production. LEP rs7799039 and LEPR rs1137101 genetic variants modify the serum LEP levels and PGC1A rs8192678 alters the PGC1A activity. The study objective was to explore the associations of these variants with susceptibility to MS, disease course/clinical parameters and also with peripheral blood mononuclear cell expression of the target genes and plasma LEP concentrations, in the study subjects. Methods: The study groups included 528 patients with MS and 429 controls. TaqMan® assays were used for genotyping and gene expression quantification. The Chi-square, parametric and nonparametric tests and simple/multiple logistic regression were performed for the statistical analysis of data. Results: A multiple logistic regression model including all three investigated variants, applied to patients (RRMS + SPMS) and controls, showed that PGC1A rs8192678 minor allele had an increased risk for the occurrence of disease, with OR (95%CI) = 1,32 (1,01–1,73), P = 0,04. Between-effect of gender and LEPR variant on the multiple sclerosis severity score (MSSS) was identified (P = 0,005). In male patients (relapsing-remitting and secondary progressive), LEPR minor allele carriers had increased MSSS (GG + AG vs AA, median (minimum–maximum) = 5,38 (0,64–9,88) vs 4,27 (0,78–9,63); P = 0,01, Padj = 0,03). In relapsing-remitting patients LEP rs7799039 affected the LEP gene expression (P = 0,006; Padj = 0,04). Conclusion: The current findings implicate an impact of investigated genetic variants on the pathogenesis of MS. © 2021 Elsevier B.V.",
journal = "Gene",
title = "Association study of rs7799039, rs1137101 and rs8192678 gene variants with disease susceptibility/severity and corresponding LEP, LEPR and PGC1A gene expression in multiple sclerosis",
volume = "774",
pages = "145422",
doi = "10.1016/j.gene.2021.145422"
}

Kolić, I., Stojković, L. S., Stanković, A., Stefanović, M., Dinčić, E.,& Živković, M.. (2021). Association study of rs7799039, rs1137101 and rs8192678 gene variants with disease susceptibility/severity and corresponding LEP, LEPR and PGC1A gene expression in multiple sclerosis. in Gene, 774, 145422.
https://doi.org/10.1016/j.gene.2021.145422

Kolić I, Stojković LS, Stanković A, Stefanović M, Dinčić E, Živković M. Association study of rs7799039, rs1137101 and rs8192678 gene variants with disease susceptibility/severity and corresponding LEP, LEPR and PGC1A gene expression in multiple sclerosis. in Gene. 2021;774:145422.
doi:10.1016/j.gene.2021.145422 .

Kolić, Ivana, Stojković, Ljiljana S., Stanković, Aleksandra, Stefanović, Milan, Dinčić, Evica, Živković, Maja, "Association study of rs7799039, rs1137101 and rs8192678 gene variants with disease susceptibility/severity and corresponding LEP, LEPR and PGC1A gene expression in multiple sclerosis" in Gene, 774 (2021):145422,
https://doi.org/10.1016/j.gene.2021.145422 . .

TY  - JOUR
AU  - Stefanović, Milan
AU  - Životić, Ivan
AU  - Stojković, Ljiljana S.
AU  - Dinčić, Evica
AU  - Stanković, Aleksandra
AU  - Živković, Maja
PY  - 2020
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/8885
AB  - An algorithm Probabilistic Identification of Causal SNPs, identified 434 causal variants for multiple sclerosis (MS) including IL2RA rs2104286, IFI30 rs11554159 and IKZF3 rs12946510. Analysis of individual and combined effects of these variants in the Serbian population identified that Il2RA rs2104286 G allele carriers had a lower risk for developing MS (gender adjusted OR = 0.63, p = .003). With regard to the IFI30 rs11554159 recessive genetic model, among HLA-DRB1*15:01 positive patients, the AA homozygote had a significantly higher MSSS compared to the G allele carriers (p = .003). This study confirms role of IL2RA rs2104286 in MS and suggest the role of IFI30 rs11554159 in disease severity, which needs validation.
T2  - Journal of Neuroimmunology
T1  - The association of genetic variants IL2RA rs2104286, IFI30 rs11554159 and IKZF3 rs12946510 with multiple sclerosis onset and severity in patients from Serbia
VL  - 347
SP  - 577346
DO  - 10.1016/j.jneuroim.2020.577346
ER  - 

@article{
author = "Stefanović, Milan and Životić, Ivan and Stojković, Ljiljana S. and Dinčić, Evica and Stanković, Aleksandra and Živković, Maja",
year = "2020",
abstract = "An algorithm Probabilistic Identification of Causal SNPs, identified 434 causal variants for multiple sclerosis (MS) including IL2RA rs2104286, IFI30 rs11554159 and IKZF3 rs12946510. Analysis of individual and combined effects of these variants in the Serbian population identified that Il2RA rs2104286 G allele carriers had a lower risk for developing MS (gender adjusted OR = 0.63, p = .003). With regard to the IFI30 rs11554159 recessive genetic model, among HLA-DRB1*15:01 positive patients, the AA homozygote had a significantly higher MSSS compared to the G allele carriers (p = .003). This study confirms role of IL2RA rs2104286 in MS and suggest the role of IFI30 rs11554159 in disease severity, which needs validation.",
journal = "Journal of Neuroimmunology",
title = "The association of genetic variants IL2RA rs2104286, IFI30 rs11554159 and IKZF3 rs12946510 with multiple sclerosis onset and severity in patients from Serbia",
volume = "347",
pages = "577346",
doi = "10.1016/j.jneuroim.2020.577346"
}

Stefanović, M., Životić, I., Stojković, L. S., Dinčić, E., Stanković, A.,& Živković, M.. (2020). The association of genetic variants IL2RA rs2104286, IFI30 rs11554159 and IKZF3 rs12946510 with multiple sclerosis onset and severity in patients from Serbia. in Journal of Neuroimmunology, 347, 577346.
https://doi.org/10.1016/j.jneuroim.2020.577346

Stefanović M, Životić I, Stojković LS, Dinčić E, Stanković A, Živković M. The association of genetic variants IL2RA rs2104286, IFI30 rs11554159 and IKZF3 rs12946510 with multiple sclerosis onset and severity in patients from Serbia. in Journal of Neuroimmunology. 2020;347:577346.
doi:10.1016/j.jneuroim.2020.577346 .

Stefanović, Milan, Životić, Ivan, Stojković, Ljiljana S., Dinčić, Evica, Stanković, Aleksandra, Živković, Maja, "The association of genetic variants IL2RA rs2104286, IFI30 rs11554159 and IKZF3 rs12946510 with multiple sclerosis onset and severity in patients from Serbia" in Journal of Neuroimmunology, 347 (2020):577346,
https://doi.org/10.1016/j.jneuroim.2020.577346 . .