Functional PAX-6 gene-linked polymorphic region: potential association with paranoid schizophrenia

Biol Psychiatry. 1999 Jun 15;45(12):1585-91. doi: 10.1016/s0006-3223(99)00024-4.


Background: Early differentiation of the nervous system and adult CNS neuroplasticity is modulated by PAX-6. We have shown previously that a highly polymorphic, functional AC/AG repeat in the 5' regulatory region of the gene showed significantly increased promoter activity, if containing > or = 29 repeats, and that the heterozygous genotype (< or = 28/> or = 29) revealed increased mRNA PAX-6 levels in human brain tissue compared to the homozygous short variant.

Methods: In a case-control study of 655 unrelated individuals, allele frequencies and genotype distributions of the functional PAX-6 promoter polymorphism were investigated comprising patients with DSM-IV schizophrenia, patients with affective disorders, and population controls.

Results: No allelic or genotypic association of the PAX-6 promoter polymorphism to affective disorder or to schizophrenia as one disease entity was observed. After subtyping schizophrenia into paranoid and nonparanoid forms, potential evidence was found for a genotypic association of the high-activity variant with the paranoid subtype of schizophrenia (p = .02). The estimated odds ratio was 1.7 (95% CI .98 to 2.95) for those heterozygous and 1.4 (95% CI .82 to 2.42) for those heterozygous or homozygous for the high-activity variant compared to the homozygous low-activity variant.

Conclusions: Our finding indicates that early developmental genes may be involved in the etiopathogenesis of schizophrenia subtypes via variable transcriptional regulation in the developing and adult human brain.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Bipolar Disorder / genetics
  • Brain / cytology*
  • Case-Control Studies
  • Culture Techniques
  • Female
  • Genes, Regulator / genetics*
  • Genetic Linkage / genetics
  • Genetic Variation / genetics
  • Genotype
  • Heterozygote
  • Humans
  • Male
  • Middle Aged
  • Neuronal Plasticity / genetics
  • Point Mutation / genetics
  • Polymorphism, Genetic / genetics*
  • Promoter Regions, Genetic / genetics*
  • RNA, Messenger / genetics
  • Schizophrenia, Paranoid / genetics*
  • Transcription, Genetic / genetics


  • RNA, Messenger