title: The gender-specific association of EHD3 polymorphisms with major depressive disorder.
abstract: Recent work suggests that women have a higher liability to major depressive disorder (MDD) than men, but the mechanism for the gender difference remains unknown. Given a genetic component involved in MDD, genome-wide association studies (GWAS) have been performed to search for susceptibility loci for the diseases and several genes of interest have been reported, including the EH-domain containing 3 (EHD3) gene that encodes a protein participating in endosome protein trafficking. However, the polymorphism association of the EHD3 gene with MDD failed to be replicated in a Chinese Han population. In the present study, we stratified 517 MDD patients and 455 control subjects by gender and symptoms and found 3 SNPs present in the EHD3 gene, of which rs619002 and rs644926 were exclusively associated with female MDD (p=0.0045 and p=0.0074, respectively) and rs649729 (p=0.0029) was closely related to anxious mood of female patients, suggesting a gender-specific role of EHD3 in MDD. These positive findings help explain, at least from one aspect, the poor replication of GWAS results. Further functional analysis is needed to clarify how variants in EHD3 may play a female-specific role in the pathogenesis of MDD.
authors.affiliation: Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, PR China.
authors.forename: Le
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Neuropathology, Tianjin Neurologic Institute, Tianjin Medical University General Hospital, Tianjin 300052, China; Tianjin Key Laboratory of Injuries, Variations and Regeneration of the Nervous System, Tianjin 300052, China; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, China.
authors.forename: Cuijuan
authors.initials: C
authors.lastname: Shi
authors.affiliation: Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan 030001, PR China. Electronic address: krzhang_sxmu@vip.163.com.
authors.forename: Kerang
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, PR China. Electronic address: xuqi@pumc.edu.cn.
authors.forename: Qi
authors.initials: Q
authors.lastname: Xu
mesh_terms: D000328:Adult; D044466:Asian People; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000208:ethnology / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012737:Sex Factors; D055815:Young Adult
chemical_list: D002352:Carrier Proteins; C406447:EHD3 protein, human
keywords: EHD3; Female; MDD