Interaction between gamma-Aminobutyric Acid A Receptor Genes: New Evidence in Migraine Susceptibility

• Type: Article in International Scientific Journal
• Date: 2013

Authors

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

Journal

Title: PLoS ONE

Vol. 8 No. 1

Final page: e74087

ISSN: 1932-6203

Publisher: Public Library of Science

Indexing

ISI Web of Knowledge - 9 Citations

Scopus - 13 Citations

Other information

Authenticus ID: P-008-DR7

DOI: 10.1371/journal.pone.0074087

Abstract (EN): 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 (GABA(A)R) 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 GABA(A)R, all significant after permutation correction. To our knowledge, we show for the first time, the putative involvement of polymorphisms in GABA(A)R 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8