Nat.Genetics： 偏头痛与三个基因变异有关

美国研究人员6月12日在英国《自然—遗传学》杂志网络版上发表研究报告称，偏头痛与3个基因变异有关。这一发现有助于了解偏头痛的发病机制，并为以该基因为靶向开发治疗药物奠定基础。

美国布里格姆妇科医院的研究人员对超过2.3万名妇女的基因数据进行了分析，这些妇女中有5000多人患有偏头痛。在这份全基因组关联研究中，研究人员在约30亿个人类基因碱基对中，找出了具有关联性的序列。

结果显示，偏头痛患者的3个基因较常出现变异，这3个基因分别为TRPM8，LRP1和PRDM16。如果被调查女性的上述基因中的任何一个发生变异，她们患偏头痛的几率会提高10%至15%。

据研究者介绍，TRPM8基因控制着人们对寒冷和疼痛的敏感程度，LRP1基因负责向神经元传递信号。PRDM16基因能够调控肌肉脂肪代谢，其与偏头痛的关联正在研究中。

虽然偏头痛发生的确切原因不明，但普遍观点认为偏头痛与遗传因素有关。多项医学研究显示，神经细胞对刺激物的过度反应是导致偏头痛的重要原因，女性患偏头痛的几率是男性的3到4倍。

研究人员指出，尽管这一发现是偏头痛研究中的一大进展，但不足以就此下结论说偏头痛是由这3个基因变异造成的，研究人员仍需对此进行更深入的研究，以确定造成偏头痛的真正原因。

MedSci推荐原文出处：

Nature Genetics     DOI:10.1038/ng.856

Genome-wide association study reveals three susceptibility loci for common migraine in the general population

Daniel I Chasman; Markus Schürks; Verneri Anttila; Boukje de Vries; Ulf Schminke; Lenore J Launer; Gisela M Terwindt; Arn M J M van den Maagdenberg; Konstanze Fendrich; Henry V?lzke; Florian Ernst; Lyn R Griffiths; Julie E Buring; Mikko Kallela; Tobias Freilinger; Christian Kubisch; Paul M Ridker; Aarno Palotie; Michel D Ferrari; Wolfgang Hoffmann; Robert Y L Zee; Tobias Kurth

Migraine is a common, heterogeneous and heritable neurological disorder. Its pathophysiology is incompletely understood, and its genetic influences at the population level are unknown. In a population-based genome-wide analysis including 5,122 migraineurs and 18,108 non-migraineurs, rs2651899 (1p36.32, PRDM16), rs10166942 (2q37.1, TRPM8) and rs11172113 (12q13.3, LRP1) were among the top seven associations (P < 5 × 10?6) with migraine. These SNPs were significant in a meta-analysis among three replication cohorts and met genome-wide significance in a meta-analysis combining the discovery and replication cohorts (rs2651899, odds ratio (OR) = 1.11, P = 3.8 × 10?9; rs10166942, OR = 0.85, P = 5.5 × 10?12; and rs11172113, OR = 0.90, P = 4.3 × 10?9). The associations at rs2651899 and rs10166942 were specific for migraine compared with non-migraine headache. None of the three SNP associations was preferential for migraine with aura or without aura, nor were any associations specific for migraine features. TRPM8 has been the focus of neuropathic pain models, whereas LRP1 modulates neuronal glutamate signaling, plausibly linking both genes to migraine pathophysiology.