title: Genetic association and gene expression studies suggest that genetic variants in the SYNE1 and TNF genes are related to menstrual migraine.
abstract: BACKGROUND
  Menstrual migraine (MM) encompasses pure menstrual migraine (PMM) and menstrually-related migraine (MRM). This study was aimed at investigating genetic variants that are potentially related to MM, specifically undertaking genotyping and mRNA expression analysis of the ESR1, PGR, SYNE1 and TNF genes in MM cases and non-migraine controls.
  
  
  METHODS
  A total of 37 variants distributed across 14 genes were genotyped in 437 DNA samples (282 cases and 155 controls). In addition levels of gene expression were determined in 74 cDNA samples (41 cases and 33 controls). Association and correlation analysis were performed using Plink and RStudio.
  
  
  RESULTS
  SNPs rs3093664 and rs9371601 in TNF and SYNE1 genes respectively, were significantly associated with migraine in the MM population (p = 0.008; p = 0.009 respectively). Analysis of qPCR results found no significant difference in levels of gene expression between cases and controls. However, we found a significant correlation between the expression of ESR1 and SYNE1, ESR1 and PGR and TNF and SYNE1 in samples taken during the follicular phase of the menstrual cycle.
  
  
  CONCLUSIONS
  Our results show that SNPs rs9371601 and rs3093664 in the SYNE1 and TNF genes respectively, are associated with MM. The present study also provides strong evidence to support the correlation of ESR1, PGR, SYNE1 and TNF gene expression in MM.
authors.forename: Astrid J
authors.initials: AJ
authors.lastname: Rodriguez-Acevedo
authors.forename: Robert A
authors.initials: RA
authors.lastname: Smith
authors.forename: Bishakha
authors.initials: B
authors.lastname: Roy
authors.forename: Heidi
authors.initials: H
authors.lastname: Sutherland
authors.forename: Rod A
authors.initials: RA
authors.lastname: Lea
authors.forename: Alison
authors.initials: A
authors.lastname: Frith
authors.forename: E Anne
authors.initials: EA
authors.lastname: MacGregor
authors.affiliation: Genomics Research Centre, Institute of Health and Biomedical Innovation, Queensland University of Technology, Musk Ave, Kelvin Grove, Brisbane, QLD 4059, Australia. lyn.griffiths@qut.edu.au.
authors.forename: Lyn R
authors.initials: LR
authors.lastname: Griffiths
mesh_terms: D000328:Adult; D003598:Cytoskeletal Proteins; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008599:Menstruation Disturbances / Q000235:genetics*; D008875:Middle Aged; D008881:Migraine Disorders / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D055815:Young Adult
chemical_list: D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C415465:SYNE1 protein, human; D014409:Tumor Necrosis Factor-alpha