Fernandez F, Lea R A, Colson N J, Bellis C, Quinlan S, Griffiths L R
Genomics Research Centre, School of Medical Science, Griffith University, Gold Coast, Queensland, Australia.
J Neurol Sci. 2006 Dec 21;251(1-2):118-23. doi: 10.1016/j.jns.2006.09.013. Epub 2006 Nov 7.
Migraine is a debilitating neurological disorder, affecting 12% of Caucasian populations. It is well known that migraine has a strong genetic component, although the type and number of genes involved is unclear. Our previous work has investigated dopamine related migraine candidate genes and has reported a significant allelic association with migraine of a microsatellite localised to the promoter region of the dopamine beta-hydroxylase (DBH) gene. The present study performed an association analysis in a larger population of case-controls (275 unrelated Caucasian migraineurs versus 275 controls) examining two different genetic DBH polymorphisms (a functional insertion/deletion promoter and a coding SNP A444G polymorphism). Although no significant association was found for the SNP polymorphism, the results showed a significant association between the insertion/deletion variant and disease (chi(2)=8.92, P=0.011), in particular in migraine with aura (chi(2)=11.53, P=0.003) compared to the control group. Furthermore, the analysis of this polymorphism stratified by gender, revealed that male individuals with the homozygote deletion genotype had three times the risk of developing migraine, compared to females. The DBH insertion/deletion polymorphism is in linkage disequilibrium with the previously reported migraine associated DBH microsatellite and this insertion/deletion polymorphism is functional, which may explain a potential role in susceptibility to migraine.
偏头痛是一种使人衰弱的神经系统疾病，影响着12%的白种人。众所周知，偏头痛具有很强的遗传成分，尽管涉及的基因类型和数量尚不清楚。我们之前的工作研究了与多巴胺相关的偏头痛候选基因，并报告了一个位于多巴胺β-羟化酶（DBH）基因启动子区域的微卫星与偏头痛存在显著的等位基因关联。本研究在更大的病例对照人群（275名无亲缘关系的白种人偏头痛患者与275名对照）中进行了关联分析，检测了两种不同的DBH基因多态性（一种功能性插入/缺失启动子和一种编码SNP A444G多态性）。尽管未发现SNP多态性有显著关联，但结果显示插入/缺失变异与疾病之间存在显著关联（χ²=8.92，P=0.011），特别是与对照组相比，在伴有先兆的偏头痛中（χ²=11.53，P=0.003）。此外，按性别对该多态性进行分层分析发现，与女性相比，具有纯合子缺失基因型的男性个体患偏头痛的风险是女性的三倍。DBH插入/缺失多态性与先前报道的与偏头痛相关的DBH微卫星处于连锁不平衡状态，且这种插入/缺失多态性具有功能性，这可能解释了其在偏头痛易感性中的潜在作用。
