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

Background: Early differentiation of the nervous system and adult CNS neuro plasticity is modulated by PAX-6 We have shown previously that a highly pol ymorphic, functional AC/AG repeat in the 5' regulatory region of the gene s howed significantly increased promoter activity, if containing greater than or equal to 29 repeats, and that the heterozygous genotype (less than or e qual to 28/less than or equal to 29) revealed increased mRNA PAX-6 levels i n human brain tissue compared to the homozygous short variant. Methods: In a case-control study of 655 unrelated individuals, allele frequ encies and genotype distributions of the functional PAX-6 promoter polymorp hism were investigated comprising patients with DSM-IV schizophrenia, patie nts with affective disorders, and population controls, Results: No allelic or genotypic association of the PAX-6 promoter polymorp hism to affective disorder or to schizophrenia as one disease entity was ob served After subtyping schizophrenia into paranoid and nonparanoid forms, p otential evidence was found for a genotypic association of the high-activit y variant with the paranoid subtype of schizophrenia (p = .02). The estimat ed odds ratio was 1.7 (95% Cl .98 to 2.95) for those heterozygous and 1.4 ( 95% Cl.82 to 2.42) for those heterozygous or homozygous for the high-activi ty variant compared to the homozygous low-activity variant. Conclusions: Our finding indicates that early developmental genes may be in volved in the etiopathogenesis of schizophrenia subtypes via variable trans criptional regulation in the developing and adult human brain.