Functional PAX-6 gene-linked polymorphic region: potential association with paranoid schizophrenia.
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.
Stöber
G
G
Department of Psychiatry, University of Würzburg, Germany.
Syagailo
Y V
YV
Okladnova
O
O
Jungkunz
G
G
Knapp
M
M
Beckmann
H
H
Lesch
K P
KP
D000328:Adult; D000483:Alleles; D001714:Bipolar Disorder / Q000235:genetics; D001921:Brain / Q000166:cytology*; D016022:Case-Control Studies; D046508:Culture Techniques; D005260:Female; D005809:Genes, Regulator / Q000235:genetics*; D008040:Genetic Linkage / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009473:Neuronal Plasticity / Q000235:genetics; D017354:Point Mutation / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012563:Schizophrenia, Paranoid / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics
D012333:RNA, Messenger