Detailed analysis of PRODH and PsPRODH reveals no association with schizophrenia

People with deletion of the chromosome 22q11 region associated with velo cardiofacial syndrome (VCFS) have a remarkably high risk of developing schizophrenia. Recently, the gene proline dehydrogenase (PRODH) which maps to 22q11 and is also an excellent functional candidate gene for psychosis, has been reported to show genetic association with schizophrenia. We have screened all the exons and adjacent intronic sequences of PRODH for the presence of sequence variation in 14 DSM IV schizophrenic subjects. Similarly, we also screened all putative exons of a sequence that is similar to proline dehydrogenase (PsPRODH) and which also maps within the deleted region. A total of nine single nucleotide polymorphisms (SNPs) were identified in PRODH, eight of which were exonic, while in PsPRODH, five SNPs were identified, one of which was in a putative exon. All samples were tested for association in a pooled sample of 368 DSM IV diagnosed schizophrenic subjects and 368 matched controls. None of the variants identified in PRODH gave even modest evidence for allelic association (P <0.1). In PsPRODH, two variants (-3864G > A and 226G > A) gave P values < 0.1. These were individually genotyped in the same subjects that had been used to construct the pools. Although a trend for association was confirmed, neither showed evidence for association at the P < 0.05 level. These results do not suggest that PRODH or PsPRODH contribute to the aetiology of schizophrenia, and that the putative schizophrenia susceptibility gene in 22q11 remains unknown. (C) 2003 Wiley-Liss, Inc.