Fernandez Francesca, Esposito Teresa, Lea Rod A, Colson Natalie J, Ciccodicola Alfredo, Gianfrancesco Fernando, Griffiths Lyn R
Genomics Research Centre, Griffith Institute for Health and Medical Research, Griffith University, Gold Coast, Queensland, Australia.
BMC Med Genet. 2008 Dec 16;9:109. doi: 10.1186/1471-2350-9-109.
Migraine is a neurological disorder characterized by recurrent attacks of severe headache, affecting around 12% of Caucasian populations. It is well known that migraine has a strong genetic component, although the number and type of genes involved is still unclear. Prior linkage studies have reported mapping of a migraine gene to chromosome Xq 24-28, a region containing a cluster of genes for GABA A receptors (GABRE, GABRA3, GABRQ), which are potential candidate genes for migraine. The GABA neurotransmitter has been implicated in migraine pathophysiology previously; however its exact role has not yet been established, although GABA receptors agonists have been the target of therapeutic developments. The aim of the present research is to investigate the role of the potential candidate genes reported on chromosome Xq 24-28 region in migraine susceptibility. In this study, we have focused on the subunit GABA A receptors type epsilon (GABRE) and type theta (GABRQ) genes and their involvement in migraine.
We have performed an association analysis in a large population of case-controls (275 unrelated Caucasian migraineurs versus 275 controls) examining a set of 3 single nucleotide polymorphisms (SNPs) in the coding region (exons 3, 5 and 9) of the GABRE gene and also the I478F coding variant of the GABRQ gene.
Our study did not show any association between the examined SNPs in our test population (P>0.05).
Although these particular GABA receptor genes did not show positive association, further studies are necessary to consider the role of other GABA receptor genes in migraine susceptibility.
偏头痛是一种神经系统疾病，其特征为严重头痛反复发作，影响约12%的白种人群。众所周知，偏头痛具有很强的遗传成分，尽管所涉及基因的数量和类型仍不清楚。先前的连锁研究报告称，一个偏头痛基因定位于Xq 24 - 28染色体，该区域包含一组γ-氨基丁酸A受体（GABRE、GABRA3、GABRQ）基因，它们是偏头痛的潜在候选基因。γ-氨基丁酸神经递质先前已被认为与偏头痛的病理生理学有关；然而，其确切作用尚未确定，尽管γ-氨基丁酸受体激动剂一直是治疗开发的靶点。本研究的目的是调查Xq 24 - 28染色体区域报道的潜在候选基因在偏头痛易感性中的作用。在本研究中，我们重点关注了γ-氨基丁酸A受体ε型（GABRE）和θ型（GABRQ）亚基基因及其与偏头痛的关系。
我们在一大组病例对照人群（275名无亲缘关系的白种偏头痛患者与275名对照）中进行了关联分析，检测了GABRE基因编码区（外显子3、5和9）的一组3个单核苷酸多态性（SNP）以及GABRQ基因的I478F编码变体。
我们的研究在测试人群中未显示所检测的SNP之间存在任何关联（P>0.05）。
尽管这些特定的γ-氨基丁酸受体基因未显示出正相关，但仍需要进一步研究以考虑其他γ-氨基丁酸受体基因在偏头痛易感性中的作用。
