Non-coding variants in VAMP2 and SNAP25 affect gene expression: potential implications in migraine susceptibility

The Journal of Headache and Pain

Brief Report

Estefânia Carvalho¹  Andreia Dias¹  Carolina Lemos¹  Miguel Alves-Ferreira²  Sandra Martins³  Alexandra M. Lopes⁴  Nádia Pinto⁵  Daniela Felício⁶  Mariana Santos⁷ 

[1] Instituto de Investigação e Inovação em Saúde (i3S), 4200-135, Porto, Portugal;ICBAS - School of Medicine and Biomedical Sciences, Universidade Do Porto, 4050-313, Porto, Portugal;Unit for Genetic and Epidemiological Research in Neurological Diseases (UnIGENe), Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, 4200-135, Porto, Portugal;Instituto de Investigação e Inovação em Saúde (i3S), 4200-135, Porto, Portugal;ICBAS - School of Medicine and Biomedical Sciences, Universidade Do Porto, 4050-313, Porto, Portugal;Unit for Genetic and Epidemiological Research in Neurological Diseases (UnIGENe), Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, 4200-135, Porto, Portugal;Centre for Predictive and Preventive Genetics (CGPP), Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, 4200-135, Porto, Portugal;Instituto de Investigação e Inovação em Saúde (i3S), 4200-135, Porto, Portugal;Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135, Porto, Portugal;Instituto de Investigação e Inovação em Saúde (i3S), 4200-135, Porto, Portugal;Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135, Porto, Portugal;Centre for Predictive and Preventive Genetics (CGPP), Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, 4200-135, Porto, Portugal;Instituto de Investigação e Inovação em Saúde (i3S), 4200-135, Porto, Portugal;Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135, Porto, Portugal;Centro de Matemática da Universidade do Porto (CMUP), 4169-007, Porto, Portugal;Instituto de Investigação e Inovação em Saúde (i3S), 4200-135, Porto, Portugal;Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135, Porto, Portugal;ICBAS - School of Medicine and Biomedical Sciences, Universidade Do Porto, 4050-313, Porto, Portugal;Instituto de Investigação e Inovação em Saúde (i3S), 4200-135, Porto, Portugal;Unit for Genetic and Epidemiological Research in Neurological Diseases (UnIGENe), Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, 4200-135, Porto, Portugal;

关键词: Migraine;    Reporter gene assays;    SNARE complex;    Non-coding variants;    VAMP2;    SNAP25;    STX1A;    Gene expression;   

DOI  :  10.1186/s10194-023-01615-z

 received in 2023-05-15, accepted in 2023-06-19,  发布年份 2023

来源: Springer

【 摘 要 】

Migraine is a common and complex neurological disease potentially caused by a polygenic interaction of multiple gene variants. Many genes associated with migraine are involved in pathways controlling the synaptic function and neurotransmitters release. However, the molecular mechanisms underpinning migraine need to be further explored.Recent studies raised the possibility that migraine may arise from the effect of regulatory non-coding variants. In this study, we explored the effect of candidate non-coding variants potentially associated with migraine and predicted to lie within regulatory elements: VAMP2_rs1150, SNAP25_rs2327264, and STX1A_rs6951030. The involvement of these genes, which are constituents of the SNARE complex involved in membrane fusion and neurotransmitter release, underscores their significance in migraine pathogenesis. Our reporter gene assays confirmed the impact of at least two of these non-coding variants. VAMP2 and SNAP25 risk alleles were associated with a decrease and increase in gene expression, respectively, while STX1A risk allele showed a tendency to reduce luciferase activity in neuronal-like cells. Therefore, the VAMP2_rs1150 and SNAP25_rs2327264 non-coding variants affect gene expression, which may have implications in migraine susceptibility. Based on previous in silico analysis, it is plausible that these variants influence the binding of regulators, such as transcription factors and micro-RNAs. Still, further studies exploring these mechanisms would be important to shed light on the association between SNAREs dysregulation and migraine susceptibility.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

Fig. 13