Novel polymorphisms of the AP-2 gene (6p24): Analysis of association with schizophrenia

The transcription factor activator protein 2 (AP-2) gene is a possible cand idate gene for schizophrenia, since it maps near D6S470, a marker on chromo some 6p24 that provided evidence of Linkage to schizophrenia. In the presen t study we analyzed the promoter region and the whole coding region of the human AP-2 gene in order to identify genetic variations that may lead to th e modification of AP-2 expression or the alteration of protein function, co ntributing to schizophrenia or particular schizophrenic phenotypes. Genomic DNA was isolated from the whole blood samples of 87 unrelated schizophreni cs and 100 healthy controls. Polymerase chain reaction (PCR) was performed, using 15 primer sets that spanned the promoter region and the whole coding region, and amplified products were screened by single-strand conformation al polymorphism (SSCP) analysis. Aberrant SSCP patterns were analyzed by di rect sequencing. Three novel polymorphisms were found in the promoter regio n; two relatively common (-90G-->C, -803G-->T) and one rare (-1769C-->A). P olymorphic status at both loci suggested strong linkage disequilibrium betw een the -90G and -803G alleles, and between the -90C and -803T alleles. Alt hough no significant differences in genotypic and allelic frequencies at th e -90 and -803 loci were found between patients and controls, significant d ifferences in the distribution of genotypes at the -90 (P = 0.008) and -803 (P = 0.037) loci were observed in patients with an episodic course compare d with controls, However, the difference for the -803 locus was not signifi cant after Bonferroni correction for multiple comparisons. Our data provide d no direct evidence of an association between schizophrenia and the polymo rphisms of the AP-2 gene, although the positive result at the -90 locus in schizophrenics with an episodic course is potentially interesting.