Associations of ATF4 gene polymorphisms with schizophrenia in male patients

Mei Qu, Fulei Tang, Lifang Wang, Hao Yan, Yonghua Han, Jun Yan, Weihua Yue, Dai Zhang

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Activating transcription factor 4 (ATF4) is considered as a positional candidate gene for schizophrenia due to its location at chromosome 22q13, a region linked to schizophrenia. Furthermore, as protein interaction partner of ATF4, disrupted in schizophrenia 1 (DISC1) and its signal pathway implicated in the pathophysiology of schizophrenia have been widely supported by a number of genetic and neurobiological studies. Our aim was to investigate whether ATF4 is associated with schizophrenia in case-control samples of Han Chinese subjects consisting of 352 schizophrenia patients and 357 healthy controls. We detected 18 single nucleotide polymorphisms (SNPs) in ATF4 locus, two of which were analyzed, including one insertion at the putative core promoter region (rs17001266, -/C) and one nonsynonymous variant in exon 1 (rs4894, C/A, Pro22Gln). Allele distributions of two SNPs showed significant associations with schizophrenia in male subjects (respectively, rs17001266: P = 0.021, OR = 1.58, 95% CI = 1.07-2.33; rs4894: P = 0.004, OR = 1.78, 95% CI = 1.19-2.67), but not in female subjects as well as the entire population. Two haplotypes CC and -A constructed of rs17001266-rs4894 also revealed significant associations with schizophrenia in male group (global P = 0.0097). These findings support that ATF4 gene may be involved in susceptibility to schizophrenia with sex-dependent effect in the Chinese Han population and suggest that further functional assays are needed to verify their relevance to the pathogenesis of schizophrenia.

Original languageEnglish (US)
Pages (from-to)732-736
Number of pages5
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume147
Issue number6
DOIs
StatePublished - Sep 5 2008
Externally publishedYes

Keywords

  • Activating transcription factor 4 (ATF4)
  • Genetic association
  • Haplotype

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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