Association between MEF2 family gene polymorphisms and susceptibility to multiple sclerosis in Chinese population.
MEF2C
MEF2D
Multiple sclerosis
Single nucleotide polymorphism
Journal
Acta neurologica Belgica
ISSN: 2240-2993
Titre abrégé: Acta Neurol Belg
Pays: Italy
ID NLM: 0247035
Informations de publication
Date de publication:
12 Aug 2023
12 Aug 2023
Historique:
received:
12
05
2023
accepted:
31
07
2023
medline:
13
8
2023
pubmed:
13
8
2023
entrez:
12
8
2023
Statut:
aheadofprint
Résumé
Multiple sclerosis (MS) is an autoimmune disease characterized by inflammatory demyelinating lesions in the white matter of the central nervous system. Myocyte enhancer factor 2 (MEF2) family genes play important roles in the immune response. This study focuses on the relationship between MEF2 family gene polymorphisms and MS. A total of 174 MS patients and 120 healthy controls were recruited. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to analyze the gene polymorphisms of MEF2D and MEF2C. In addition, peripheral blood was collected and leukocytes were isolated. The transcription level of MEF2D in the two groups of samples was detected with quantitative real time polymerase chain reaction (qRT-PCR). We found that the C allele frequency and CC genotype frequency of rs2274316 in MEF2D were significantly higher in MS patients. The C allele and CT genotype distribution for rs3790455 were significantly more frequent in MS patients. Female patients showed higher CC genotype frequency of rs2274316. The genotype frequency distribution of rs2274316 and rs3790455 were not related to onset age and phenotype of MS patients. In addition, this study also proved that MEF2D was significantly overexpressed in the peripheral blood leukocytes of MS patients. The transcription level of MEF2D was significantly higher in patients with CC genotype of rs2274316. These findings suggest rs2274316 and rs3790455 of MEF2D gene are potential genetic risk factors for MS in Chinese population. The transcription level of MEF2D is also associated with susceptibility to MS and MEF2D gene polymorphisms.
Identifiants
pubmed: 37572262
doi: 10.1007/s13760-023-02357-0
pii: 10.1007/s13760-023-02357-0
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Zhejiang Basic Public Welfare Research Project
ID : LTGY23H090006
Organisme : Zhejiang Medical and Health Science and Technology Plan Project
ID : 2022489445
Informations de copyright
© 2023. The Author(s) under exclusive licence to Belgian Neurological Society.
Références
The Lancet N (2021) Multiple sclerosis under the spotlight. Lancet Neurol 20:497. https://doi.org/10.1016/s1474-4422(21)00170-8
doi: 10.1016/s1474-4422(21)00170-8
Golalipour M, Maleki Z, Farazmandfar T, Shahbazi M (2017) PER3 VNTR polymorphism in Multiple Sclerosis: a new insight to impact of sleep disturbances in MS. Mult Scler Relat Disord 17:84–86. https://doi.org/10.1016/j.msard.2017.07.005
doi: 10.1016/j.msard.2017.07.005
pubmed: 29055480
Magyari M, Sorensen PS (2019) The changing course of multiple sclerosis: rising incidence, change in geographic distribution, disease course, and prognosis. Curr Opin Neurol 32:320–326. https://doi.org/10.1097/wco.0000000000000695
doi: 10.1097/wco.0000000000000695
pubmed: 30925518
International Multiple Sclerosis Genetics Consortium (2019) Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility. Science. https://doi.org/10.1126/science.aav7188
doi: 10.1126/science.aav7188
pmcid: 7241648
Al Jumah M, Kojan S, Al Shehri AM et al (2018) HLA class II polymorphism in Saudi patients with multiple sclerosis. Hla 91(1):17–22. https://doi.org/10.1111/tan.13173
doi: 10.1111/tan.13173
pubmed: 29131543
Rojas OL, Rojas-Villarraga A, Cruz-Tapias P et al (2010) HLA class II polymorphism in Latin American patients with multiple sclerosis. Autoimmun Rev 9(6):407–413. https://doi.org/10.1016/j.autrev.2009.11.001
doi: 10.1016/j.autrev.2009.11.001
pubmed: 19896562
Becker KG (2004) The common variants/multiple disease hypothesis of common complex genetic disorders. Med Hypotheses 62:309–317. https://doi.org/10.1016/s0306-9877(03)00332-3
doi: 10.1016/s0306-9877(03)00332-3
pubmed: 14962646
Zhao X, Di Q, Liu H et al (2022) MEF2C promotes M1 macrophage polarization and Th1 responses. Cell Mol Immunol 19:540–553. https://doi.org/10.1038/s41423-022-00841-w
doi: 10.1038/s41423-022-00841-w
pubmed: 35194174
pmcid: 8975968
Ustiugova AS, Korneev KV, Kuprash DV et al (2019) Functional SNPs in the Human Autoimmunity-Associated Locus 17q12-21. Genes. https://doi.org/10.3390/genes10020077
doi: 10.3390/genes10020077
pubmed: 30678091
pmcid: 6409600
Barker SJ, Raju RM, Milman NEP et al (2021) MEF2 is a key regulator of cognitive potential and confers resilience to neurodegeneration. Sci Transl Med 13:eabd7695. https://doi.org/10.1126/scitranslmed.abd7695
doi: 10.1126/scitranslmed.abd7695
pubmed: 34731014
pmcid: 9258338
Achiron A, Grotto I, Balicer R, Magalashvili D, Feldman A, Gurevich M (2010) Microarray analysis identifies altered regulation of nuclear receptor family members in the pre-disease state of multiple sclerosis. Neurobiol Dis 38:201–209. https://doi.org/10.1016/j.nbd.2009.12.029
doi: 10.1016/j.nbd.2009.12.029
pubmed: 20079437
Mitkin NA, Muratova AM, Schwartz AM, Kuprash DV (2016) The a allele of the single-nucleotide polymorphism rs630923 creates a binding site for MEF2C Resulting in Reduced CXCR5 Promoter Activity in B-Cell Lymphoblastic Cell Lines. Front Immunol 7:515. https://doi.org/10.3389/fimmu.2016.00515
doi: 10.3389/fimmu.2016.00515
pubmed: 27909439
pmcid: 5112242
Finch DK, Ettinger R, Karnell JL, Herbst R, Sleeman MA (2013) Effects of CXCL13 inhibition on lymphoid follicles in models of autoimmune disease. Eur J Clin Invest 43(5):501–509. https://doi.org/10.1111/eci.12063
doi: 10.1111/eci.12063
pubmed: 23517338
Han Y, Yang Y, Zhang X, Yan C, Xi S, Kang J (2007) Relationship of the CAG repeat polymorphism of the MEF2A gene and coronary artery disease in a Chinese population. Clin Chem lab Med 45:987–992. https://doi.org/10.3389/10.1515/cclm.2007.159
doi: 10.3389/10.1515/cclm.2007.159
pubmed: 17579569
Wang X, Lopez OL, Sweet RA et al (2015) Genetic determinants of disease progression in Alzheimer’s disease. J Alzheimers Dis 43:649–655. https://doi.org/10.3233/jad-140729
doi: 10.3233/jad-140729
pubmed: 25114068
pmcid: 4245313
Sunderaraman P, Cosentino S, Schupf N, Manly J, Gu Y, Barral S (2021) MEF2C common genetic variation is associated with different aspects of cognition in non-hispanic white and caribbean hispanic non-demented older adults. Front Genet 12:642327. https://doi.org/10.3389/fgene.2021.642327
doi: 10.3389/fgene.2021.642327
pubmed: 34386032
pmcid: 8353395
Fu X, Yang J, Wu X et al (2019) Association between PRDM16, MEF2D, TRPM8, LRP1 gene polymorphisms and migraine susceptibility in the She ethnic population in China. Clin Invest Med 42:E21-e30. https://doi.org/10.25011/cim.v42i1.32389
doi: 10.25011/cim.v42i1.32389
pubmed: 30904033
An XK, Fang J, Yu ZZ et al (2017) Multilocus analysis reveals three candidate genes for Chinese migraine susceptibility. Clin Genet 92:143–149. https://doi.org/10.1111/cge.12962
doi: 10.1111/cge.12962
pubmed: 28058730
González-Jiménez A, López-Cotarelo P, Agudo-Jiménez T et al (2022) Unraveling the Influence of HHEX Risk Polymorphism rs7923837 on Multiple Sclerosis Pathogenesis. Int J Mol Sci. https://doi.org/10.3390/ijms23147956
doi: 10.3390/ijms23147956
pubmed: 35897697
pmcid: 9331056
Kurtzke JF (1983) Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 33(11):1444–1452. https://doi.org/10.1212/wnl.33.11.1444
doi: 10.1212/wnl.33.11.1444
pubmed: 6685237
Ran C, Graae L, Magnusson PK, Pedersen NL, Olson L, Belin AC (2014) A replication study of GWAS findings in migraine identifies association in a Swedish case-control sample. BMC Med Genet 15:38. https://doi.org/10.1186/1471-2350-15-38
doi: 10.1186/1471-2350-15-38
pubmed: 24674449
pmcid: 3986694
Chen X, Gao B, Ponnusamy M, Lin Z, Liu J (2017) MEF2 signaling and human diseases. Oncotarget 8:112152–112165. https://doi.org/10.18632/oncotarget.22899
doi: 10.18632/oncotarget.22899
pubmed: 29340119
pmcid: 5762387
Shalizi AK, Bonni A (2005) brawn for brains: the role of MEF2 proteins in the developing nervous system. Curr Top Dev Biol 69:239–266. https://doi.org/10.1016/s0070-2153(05)69009-6
doi: 10.1016/s0070-2153(05)69009-6
pubmed: 16243602
Lioudyno V, Abdurasulova I, Tatarinov A et al (2020) The effect of galanin gene polymorphism rs948854 on the severity of multiple sclerosis: A significant association with the age of onset. Mult Scler Relat Disord 37:101439. https://doi.org/10.1016/j.msard.2019.101439
doi: 10.1016/j.msard.2019.101439
pubmed: 32173003
Laursen JH, Søndergaard HB, Sørensen PS, Sellebjerg F, Oturai AB (2016) Association between age at onset of multiple sclerosis and vitamin D level-related factors. Neurology 86:88–93. https://doi.org/10.1212/wnl.0000000000002075
doi: 10.1212/wnl.0000000000002075
pubmed: 26446064
Xing W, Hong M, Wei Z, Zhang W (2022) Correlation between ERα gene polymorphism and multiple sclerosis and neuromyelitis optica. Medicine 101:e31126. https://doi.org/10.1097/md.0000000000031126
doi: 10.1097/md.0000000000031126
pubmed: 36254093
pmcid: 9575784
Lioudyno V, Abdurasulova I, Bisaga G, Skulyabin D, Klimenko V (2017) Single-nucleotide polymorphism rs948854 in human galanin gene and multiple sclerosis: a gender-specific risk factor. J Neurosci Res 95:644–651. https://doi.org/10.1002/jnr.23887
doi: 10.1002/jnr.23887
pubmed: 27870457
Stuart R, Lovett-Racke AE, Frohman EM, Hawker K, Racke MK (2007) Genetic analysis of the exon 1 position 49 CD152 dimorphism in multiple sclerosis. J Neuroimmunol 191(1–2):45–50. https://doi.org/10.1016/j.jneuroim.2007.09.008
doi: 10.1016/j.jneuroim.2007.09.008
pubmed: 17920697
pmcid: 2812429
Jamshidian A, Nikseresht AR, Vessal M, Kamali-Sarvestani E (2010) Association of CD1A +622 T/C, +737 G/C and CD1E +6129 A/G genes polymorphisms with multiple sclerosis. Immunol Invest 39(8):874–889. https://doi.org/10.3109/08820139.2010.503768
doi: 10.3109/08820139.2010.503768
pubmed: 20954848
Farias FHG, Dahlqvist J, Kozyrev SV et al (2019) A rare regulatory variant in the MEF2D gene affects gene regulation and splicing and is associated with a SLE sub-phenotype in Swedish cohorts. Eur J Hum Genet 27:432–441. https://doi.org/10.1038/s41431-018-0297-x
doi: 10.1038/s41431-018-0297-x
pubmed: 30459414
Qing J, Li C, Hu X et al (2022) Differentiation of T Helper 17 cells may mediate the abnormal humoral immunity in IgA nephropathy and inflammatory bowel disease based on shared genetic effects. Front Immunol 13:916934. https://doi.org/10.3389/fimmu.2022.916934
doi: 10.3389/fimmu.2022.916934
pubmed: 35769467
pmcid: 9234173
Kim YJ, Oh J, Jung S (2023) The transcription factor Mef2d regulates B: T synapse-dependent GC-T(FH) differentiation and IL-21-mediated humoral immunity. Sci Immunol 8(81):eadf2248. https://doi.org/10.1126/sciimmunol.adf2248
doi: 10.1126/sciimmunol.adf2248
pubmed: 36961907
Martínez-Aguilar L, Pérez-Ramírez C, Maldonado-Montoro MDM et al (2020) Effect of genetic polymorphisms on therapeutic response in multiple sclerosis relapsing-remitting patients treated with interferon-beta. Mutat Res Rev Mutat Res 785:108322. https://doi.org/10.1016/j.mrrev.2020.108322
doi: 10.1016/j.mrrev.2020.108322
pubmed: 32800273
Zhang Y, Liu J, Wang C, Liu J, Lu W (2021) Toll-Like Receptors Gene Polymorphisms in Autoimmune Disease. Front Immunol 12:672346. https://doi.org/10.3389/fimmu.2021.672346
doi: 10.3389/fimmu.2021.672346
pubmed: 33981318
pmcid: 8107678