title: New evidence for involvement of ESR1 gene in susceptibility to Chinese migraine.
abstract: Migraine is a common and disabling nervous system disease with a significant genetic predisposition. The sex hormones play an important role in the pathogenesis of migraine. However, the conclusions of the previous genetic relation studies are conflicting. The aim of this study is to determine whether variants in genes involved in estrogen receptor and estrogen hormone metabolism are related to Chinese migraine. By employing a case-control approach, 8 SNPs in the ESR1, ESR2, and CYP19A1 genes are studied in a cohort of 494 migraine cases and 533 controls. In addition, genotyping is performed using Sequenom MALDI-TOF mass spectrometry iPLEX platform. Univariate and multivariate analyses are carried out by logistic regression. The corresponding haplotypes are studied with the Haploview software and gene-gene interaction is assessed using the Generalized Multifactor Dimensionality Reduction (GMDR) analysis. There are significant differences in allelic distributions for rs2234693 and rs9340799 in ESR1 gene between patients with migraine and control subjects. Univariate logistic analysis shows that rs2234693 and rs9340799 are risk factors for migraine, but multivariate analysis reveals that only rs2234693 is significant associated with migraine. In the subgroup analysis, rs2234693 in ESR1 gene is found associated with menstrually related migraine. Further haplotypic analysis shows that rs2234693-rs9340799 TA haplotype serves as risk haplotype for migraine. The GMDR analysis identifies rs2234693 in ESR1 alone to be a crucial candidate in migraine susceptibility. This study is in agreement with the previous studies that variants in the ESR1 gene are associated with migraine suggesting that it plays a role in the migraine process.
authors: Department of Neurology, The First Affiliated Hospital of Xiamen University, Xiamen, China.
authors: Xingkai
authors: X
authors: An
authors: Department of Neurology, The First Affiliated Hospital of Xiamen University, Xiamen, China.
authors: Jie
authors: J
authors: Fang
authors: Department of Neurology, The First Affiliated Hospital of Xiamen University, Xiamen, China.
authors: Qing
authors: Q
authors: Lin
authors: Department of Neurology, The First Affiliated Hospital of Xiamen University, Xiamen, China.
authors: Congxia
authors: C
authors: Lu
authors: Department of Neurology, The First Affiliated Hospital of Xiamen University, Xiamen, China. xmqilinma@hotmail.com.|The First Clinical Medical College of Fujian Medical University, Fuzhou, China. xmqilinma@hotmail.com.
authors: Qilin
authors: Q
authors: Ma
authors: Department of Neurology, The First Affiliated Hospital of Xiamen University, Xiamen, China. xmhongliqu@hotmail.com.
authors: Hongli
authors: H
authors: Qu
mesh_terms: D000328:Adult; D001141:Aromatase / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002681:China; D047628:Estrogen Receptor alpha / Q000235:genetics*; D047629:Estrogen Receptor beta / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D006801:Humans; D016015:Logistic Models; D008297:Male; D008881:Migraine Disorders / Q000235:genetics*; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: C506487:ESR1 protein, human; C000600034:ESR2 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D001141:Aromatase; C561410:CYP19A1 protein, human
keywords: CYP19A1; China; ESR1; ESR2; Migraine; Polymorphism