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多位点分析揭示了三个中国偏头痛易感性候选基因。

Multilocus analysis reveals three candidate genes for Chinese migraine susceptibility.

作者信息

An X-K, Fang J, Yu Z-Z, Lin Q, Lu C-X, Qu H-L, Ma Q-L

机构信息

Department of Neurology, The First Affiliated Hospital of Xiamen University, Xiamen, China.

First Clinical Medical College, The First Clinical Medical College of Fujian Medical University, Fuzhou, China.

出版信息

Clin Genet. 2017 Aug;92(2):143-149. doi: 10.1111/cge.12962. Epub 2017 Feb 22.

DOI:10.1111/cge.12962
PMID:28058730
Abstract

Several genome-wide association studies (GWASs) in Caucasian populations have identified 12 loci that are significantly associated with migraine. More evidence suggests that serotonin receptors are also involved in migraine pathophysiology. In the present study, a case-control study was conducted in a cohort of 581 migraine cases and 533 ethnically matched controls among a Chinese population. Eighteen polymorphisms from serotonin receptors and GWASs were selected, and genotyping was performed using a Sequenom MALDI-TOF mass spectrometry iPLEX platform. The genotypic and allelic distributions of MEF2D rs2274316 and ASTN2 rs6478241 were significantly different between migraine patients and controls. Univariate and multivariate analysis revealed significant associations of polymorphisms in the MEF2D and ASTN2 genes with migraine susceptibility. MEF2D, PRDM16 and ASTN2 were also found to be associated with migraine without aura (MO) and migraine with family history. And, MEF2D and ASTN2 also served as genetic risk factors for the migraine without family history. The generalized multifactor dimensionality reduction analysis identified that MEF2D and HTR2E constituted the two-factor interaction model. Our study suggests that the MEF2D, PRDM16 and ASTN2 genes from GWAS are associated with migraine susceptibility, especially MO, among Chinese patients. It appears that there is no association with serotonin receptor related genes.

摘要

多项针对高加索人群的全基因组关联研究(GWAS)已确定了12个与偏头痛显著相关的基因座。更多证据表明,血清素受体也参与偏头痛的病理生理过程。在本研究中,对一组581例偏头痛患者和533例种族匹配的对照者进行了病例对照研究,这些人均来自中国人群。从血清素受体和GWAS中选择了18个多态性位点,并使用Sequenom MALDI-TOF质谱iPLEX平台进行基因分型。偏头痛患者和对照者之间MEF2D rs2274316和ASTN2 rs6478241的基因型和等位基因分布存在显著差异。单因素和多因素分析显示,MEF2D和ASTN2基因中的多态性与偏头痛易感性显著相关。还发现MEF2D、PRDM16和ASTN2与无先兆偏头痛(MO)和有家族史的偏头痛有关。而且,MEF2D和ASTN2也是无家族史偏头痛的遗传风险因素。广义多因素降维分析确定MEF2D和HTR2E构成了双因素相互作用模型。我们的研究表明,来自GWAS的MEF2D、PRDM16和ASTN2基因与中国患者的偏头痛易感性相关,尤其是MO。似乎与血清素受体相关基因无关。

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