{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T13:46:23Z","timestamp":1776001583470,"version":"3.50.1"},"reference-count":86,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,9,26]],"date-time":"2020-09-26T00:00:00Z","timestamp":1601078400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["SFRH\/BD\/96253\/2013"],"award-info":[{"award-number":["SFRH\/BD\/96253\/2013"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["headachejournal.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Headache"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>A number of observations, including among our study population, have implicated variants in the syntaxin\u20101A, 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Migraine is a common and complex neurologic disorder that affects approximately 15\u201018% 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed a case\u2010control 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\u2010nucleotide polymorphisms in 18 genes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We found significant associations between single\u2010nucleotide variants and migraine in 7 genes,\n                      <jats:italic>SYN1<\/jats:italic>\n                      ,\n                      <jats:italic>SYN2<\/jats:italic>\n                      ,\n                      <jats:italic>SNAP25<\/jats:italic>\n                      ,\n                      <jats:italic>VAMP2<\/jats:italic>\n                      ,\n                      <jats:italic>STXBP1<\/jats:italic>\n                      ,\n                      <jats:italic>STXBP5<\/jats:italic>\n                      , and\n                      <jats:italic>UNC13A<\/jats:italic>\n                      , either conferring an increased risk or protection of migraine. Due to\n                      <jats:italic>SYN1<\/jats:italic>\n                      X\u2010chromosomal 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 (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a0.021; OR\u00a0=\u00a01.69; 95% CI: 1.21\u20102.34). In contrast, the TT genotype of the same variant emerged as a potential protective factor (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a0.003; OR\u00a0=\u00a00.45; 95% CI: 0.27\u20100.74). The\n                      <jats:italic>SYN2<\/jats:italic>\n                      analysis supported the rs3773364's G allele (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a0.014) as a risk factor for migraine, and although not statistically significant after correction, the AG genotype (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a0.006; OR\u00a0=\u00a01.86; 95% CI: 1.20\u20102.90) reinforced the allelic findings. Additionally, we found the\n                      <jats:italic>SNAP25<\/jats:italic>\n                      \u2010rs363039's CT genotype (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a0.001; OR\u00a0=\u00a02.14; 95% CI: 1.36\u20103.34), the\n                      <jats:italic>STXBP5<\/jats:italic>\n                      \u2010rs1765028's T allele (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a0.041; OR\u00a0=\u00a01.46; 95% CI: 1.13\u20101.90), and the\n                      <jats:italic>UNC13B<\/jats:italic>\n                      \u2010rs7851161's TT genotype (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a0.001; OR\u00a0=\u00a02.14; 95% CI: 1.36\u20103.34) as statistically significant risk factors for migraine liability.\n                      <jats:italic>VAMP2<\/jats:italic>\n                      \u2010rs1150's G allele revealed a risk association to migraine, not statistically significant after correction (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a0.068). Additionally, we found haplotypes in\n                      <jats:italic>SYN1<\/jats:italic>\n                      ,\n                      <jats:italic>SYN2<\/jats:italic>\n                      ,\n                      <jats:italic>STXBP1<\/jats:italic>\n                      , and\n                      <jats:italic>UNC13B<\/jats:italic>\n                      to be associated with migraine.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Overall, this study provides a new insight into migraine liability, identifying possible starting points for functional studies.<\/jats:p>\n                  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