title: Interaction between γ-aminobutyric acid A receptor genes: new evidence in migraine susceptibility.
abstract: Migraine is a common neurological episodic disorder with a female-to-male prevalence 3- to 4-fold higher, suggesting a possible X-linked genetic component. Our aims were to assess the role of common variants of gamma-aminobutyric acid A receptor (GABAAR) genes, located in the X-chromosome, in migraine susceptibility and the possible interaction between them. An association study with 188 unrelated cases and 286 migraine-free controls age- and ethnic matched was performed. Twenty-three tagging SNPs were selected in three genes (GABRE, GABRA3 and GABRQ). Allelic, genotypic and haplotypic frequencies were compared between cases and controls. We also focused on gene-gene interactions. The AT genotype of rs3810651 of GABRQ gene was associated with an increased risk for migraine (OR: 4.07; 95% CI: 1.71-9.73, p=0.002), while the CT genotype of rs3902802 (OR: 0.41; 95% CI: 0.21-0.78, p=0.006) and GA genotype of rs2131190 of GABRA3 gene (OR: 0.53; 95% CI: 0.32-0.88, p=0.013) seem to be protective factors. All associations were found in the female group and maintained significance after Bonferroni correction. We also found three nominal associations in the allelic analyses although there were no significant results in the haplotypic analyses. Strikingly, we found strong interactions between six SNPs encoding for different subunits of GABAAR, all significant after permutation correction. To our knowledge, we show for the first time, the putative involvement of polymorphisms in GABAAR genes in migraine susceptibility and more importantly we unraveled a role for novel gene-gene interactions opening new perspectives for the development of more effective treatments.
authors.affiliation: UnIGENe IBMC - Instituto de Biologia Molecular Celular, Universidade do Porto, Porto, Portugal.
authors.forename: Marlene
authors.initials: M
authors.lastname: Quintas
authors.forename: João Luís
authors.initials: JL
authors.lastname: Neto
authors.forename: José
authors.initials: J
authors.lastname: Pereira-Monteiro
authors.forename: José
authors.initials: J
authors.lastname: Barros
authors.forename: Jorge
authors.initials: J
authors.lastname: Sequeiros
authors.forename: Alda
authors.initials: A
authors.lastname: Sousa
authors.forename: Isabel
authors.initials: I
authors.lastname: Alonso
authors.forename: Carolina
authors.initials: C
authors.lastname: Lemos
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000483:Alleles; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D016000:Cluster Analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011963:Receptors, GABA-A / Q000145:classification / Q000235:genetics*; D055815:Young Adult
chemical_list: D011963:Receptors, GABA-A
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