Expression levels of GSDMB and ORMDL3 are associated with relapsing-remitting multiple sclerosis and IKZF3 rs12946510 variant
Аутори
Stefanović, MilanStojković, Ljiljana
Životić, Ivan
Dinčić, Evica
Stanković, Aleksandra
Živković, Maja
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
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 r...elapsing 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.
Кључне речи:
Multiple sclerosis / ORMDL3 / GSDMB / IKZF3 / 17q12-21 / rs12946510Извор:
Heliyon, 2024, 10, 3, e25033-Финансирање / пројекти:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia funded the research [451-03-1/ 2023–03/13]
Колекције
Институција/група
VinčaTY - 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 . .