Going Deep into Synaptic Vesicle Machinery Genes and Migraine Susceptibility - A Case-Control Association Study

• Type: Article in International Scientific Journal
• Date: 2020

Authors

Quintas, M (Author) Other; Neto, JL (Author) Other; Sequeiros, J (Author) Other; Sousa, A (Author) Other; Pereira Monteiro, J (Author) Other; Carolina Lemos (Author) ICBAS; Alonso, I (Author) Other

Journal

Title: Headache

Vol. 60

Pages: 2152-2165

ISSN: 0017-8748

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 0 Citations

Scopus - 2 Citations

Other information

Authenticus ID: P-00S-S94

DOI: 10.1111/head.13957

Abstract (EN): Objective A number of observations, including among our study population, have implicated variants in the syntaxin-1A, a component of the synaptic vesicles, in migraine susceptibility. Therefore, we hypothesize that variants in other components of the vesicle machinery are involved in migraine. Background Migraine is a common and complex neurologic disorder that affects approximately 15-18% of the general population. The exact cause of migraine is unknown; however, genetic studies have made possible substantial progress toward the identification of underlying molecular pathways. Neurotransmitters have been for long considered to have a key role in migraine pathophysiology; so we investigated common variants in genes involved in the synaptic vesicle machinery and their impact in migraine susceptibility. Methods We performed a case-control study comprising 188 unrelated patients with headache and 286 healthy controls in a population from the north of Portugal. Benefiting from the presence of linkage disequilibrium, we selected and genotyped 119 tagging single-nucleotide polymorphisms in 18 genes. Results We found significant associations between single-nucleotide variants and migraine in 7 genes,SYN1,SYN2,SNAP25,VAMP2,STXBP1,STXBP5, andUNC13A, either conferring an increased risk or protection of migraine. Due toSYN1X-chromosomal location, we performed the statistical analysis separated by gender and, in the female group, the C allele of rs5906435 increased the risk for migraine susceptibility (P = .021; OR = 1.69; 95% CI: 1.21-2.34). In contrast, the TT genotype of the same variant emerged as a potential protective factor (P = .003; OR = 0.45; 95% CI: 0.27-0.74). TheSYN2analysis supported the rs3773364's G allele (P = .014) as a risk factor for migraine, and although not statistically significant after correction, the AG genotype (P = .006; OR = 1.86; 95% CI: 1.20-2.90) reinforced the allelic findings. Additionally, we found theSNAP25-rs363039's CT genotype (P = .001; OR = 2.14; 95% CI: 1.36-3.34), theSTXBP5-rs1765028's T allele (P = .041; OR = 1.46; 95% CI: 1.13-1.90), and theUNC13B-rs7851161's TT genotype (P = .001; OR = 2.14; 95% CI: 1.36-3.34) as statistically significant risk factors for migraine liability.VAMP2-rs1150's G allele revealed a risk association to migraine, not statistically significant after correction (P = .068). Additionally, we found haplotypes inSYN1,SYN2,STXBP1, andUNC13Bto be associated with migraine. Conclusions Overall, this study provides a new insight into migraine liability, identifying possible starting points for functional studies.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 14