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Association study of rs7799039, rs1137101 and rs8192678 gene variants with disease susceptibility/severity and corresponding LEP, LEPR and PGC1A gene expression in multiple sclerosis
dc.creator | Kolić, Ivana | |
dc.creator | Stojković, Ljiljana S. | |
dc.creator | Stanković, Aleksandra | |
dc.creator | Stefanović, Milan | |
dc.creator | Dinčić, Evica | |
dc.creator | Živković, Maja | |
dc.date.accessioned | 2021-09-08T10:24:49Z | |
dc.date.available | 2021-09-08T10:24:49Z | |
dc.date.issued | 2021 | |
dc.identifier.issn | 0378-1119 | |
dc.identifier.uri | https://vinar.vin.bg.ac.rs/handle/123456789/9542 | |
dc.description.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. | en |
dc.language.iso | en | |
dc.relation | Ministry of Education, Science and Technological Development of the Republic of Serbia | |
dc.rights | restrictedAccess | |
dc.source | Gene | |
dc.subject | Gene expression | en |
dc.subject | LEP rs7799039 | en |
dc.subject | LEPR rs1137101 | en |
dc.subject | Multiple sclerosis severity | en |
dc.subject | Peripheral blood mononuclear cells | en |
dc.subject | PGC1A rs8192678 | en |
dc.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 | en |
dc.type | article | en |
dc.rights.license | ARR | |
dcterms.abstract | Стефановић, Милан; Колић, Ивана; Станковић, Aлександра; Стојковић, Љиљана; Живковић, Маја; Динчић, Евица; | |
dc.rights.holder | © 2021 Elsevier B.V. | |
dc.citation.volume | 774 | |
dc.citation.spage | 145422 | |
dc.identifier.wos | 000657682500007 | |
dc.identifier.doi | 10.1016/j.gene.2021.145422 | |
dc.identifier.pmid | 33450350 | |
dc.type.version | publishedVersion | |
dc.identifier.scopus | 2-s2.0-85099617667 |
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