No evidence for an association between variants at the proline dehydrogenase locus and schizophrenia or bipolar affective disorder

Abstract

The proline dehydrogenase locus must be considered as a positional and functional candidate in schizophrenia. It is located in the chromosomal region of the velocardiofacial syndrome on 22q11 that is suspected to contain genes relevant to schizophrenia, and is involved in the metabolism of neurotransmitters. Positive association between single-nucleotide polymorphisms at the proline dehydrogenase locus and schizophrenia further supported the role of proline dehydrogenase in the development of schizophrenia. In order to replicate these findings, we analyzed three single-nucleotide polymorphisms in a sample comprising 299 schizophrenic patients and 300 controls. In addition, we assessed whether proline dehydrogenase also contributes to bipolar affective disorder, because chromosome 22q11 is also implicated in bipolar affective disorder. We therefore included 300 patients with bipolar affective disorder. This is the first study on a potential involvement of the proline dehydrogenase locus in bipolar affective disorder. Neither single marker nor haplotype analysis revealed an association between variants at the proline dehydrogenase locus and schizophrenia or bipolar affective disorder.

Functional Polymorphisms in PRODH Are Associated with Risk and Protection for Schizophrenia and Fronto-Striatal Structure and Function

“…Li et al [8] found rs385440 and two-marker haplotypes consisting of rs385440 and rs450046 (G-G) and rs372055 and rs385440 (T-A) associated with schizophrenia in a 528 trio and sibling pair sample. Abu Jamra and colleagues [18] found no association with the three putatively non functional SNPs, rs16983466, rs372055, and rs383964, individually or in haplotypes in a German sample. Glaser et al [12] typed 4 SNPs (rs450046, rs383964, rs372055 and rs385440) in a sample of 488 Bulgarian trios.…”

“…Furthermore, a linkage peak at 22q11 has also been identified in a meta-analysis of families with multiple affect patients with schizophrenia [7]. Several recent studies have found genetic associations of schizophrenia with tag and functional single nucleotide polymorphisms (SNPs) in PRODH [8]–[11], although this association has not been observed in all samples [12]–[18]. In addition to these genetic data, hyperprolinemia has been noted in populations of psychotic patients [19]–[26] and has been associated with neurological problems in 22q11 syndrome [24].…”