Article

The PIP5K2A and RGS4 genes are differentially associated with deficit and non-deficit schizophrenia

Leiden University, Leyden, South Holland, Netherlands
Genes Brain and Behavior (Impact Factor: 3.66). 04/2007; 6(2):113-9. DOI: 10.1111/j.1601-183X.2006.00234.x
Source: PubMed

ABSTRACT

Several putative schizophrenia susceptibility genes have recently been reported, but it is not clear whether these genes are associated with schizophrenia in general or with specific disease subtypes. In a previous study, we found an association of the neuregulin 1 (NRG1) gene with non-deficit schizophrenia only. We now report an association study of four schizophrenia candidate genes in patients with and without deficit schizophrenia, which is characterized by severe and enduring negative symptoms. Single-nucleotide polymorphisms (SNPs) were genotyped in the DTNBP1 (dysbindin), G72/G30 and RGS4 genes, and the relatively unknown PIP5K2A gene, which is located in a region of linkage with both schizophrenia and bipolar disorder. The sample consisted of 273 Dutch schizophrenia patients, 146 of whom were diagnosed with deficit schizophrenia and 580 controls. The strongest evidence for association was found for the A-allele of SNP rs10828317 in the PIP5K2A gene, which was associated with both clinical subtypes (P = 0.0004 in the entire group; non-deficit P = 0.016, deficit P = 0.002). Interestingly, this SNP leads to a change in protein composition. In RGS4, the G-allele of the previously reported SNP RGS4-1 (single and as part of haplotypes with SNP RGS4-18) was associated with non-deficit schizophrenia (P = 0.03) but not with deficit schizophrenia (P = 0.79). SNPs in the DTNBP1 and G72/G30 genes were not significantly associated in any group. In conclusion, our data provide further evidence that specific genes may be involved in different schizophrenia subtypes and suggest that the PIP5K2A gene deserves further study as a general susceptibility gene for schizophrenia.

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    • "We decided to study the PIP5K2A gene, because this gene has repeatedly been shown to be associated with schizophrenia (Schwab et al., 2006; Bakker et al., 2007; He et al., 2007; Saggers- Gray et al., 2008), and the vulnerability to develop TD is related to the likelihood to develop positive symptoms of schizophrenia . In a previous study, we have confirmed this association in the presently studied Caucasian Siberian patients with schizophrenia (Fedorenko et al., 2013), but now we also demonstrated a relationship with the prevalence of TD. "
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    • "We decided to study the PIP5K2A gene, because this gene has repeatedly been shown to be associated with schizophrenia (Schwab et al., 2006; Bakker et al., 2007; He et al., 2007; Saggers- Gray et al., 2008), and the vulnerability to develop TD is related to the likelihood to develop positive symptoms of schizophrenia . In a previous study, we have confirmed this association in the presently studied Caucasian Siberian patients with schizophrenia (Fedorenko et al., 2013), but now we also demonstrated a relationship with the prevalence of TD. "
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    • "It has also been suggested that quantitative traits, such as psychopathological dimensions, may lead to a better understanding of the genotype–phenotype relationship (Tao et al. 2006; Wilcox et al. 2002). Unfortunately, only few studies have investigated whether either NRG1 or ErbB4 genes are associated with schizophrenia symptom dimensions, often with contradictory results (Bakker et al. 2004, 2007; Rethelyi et al. 2010; Middle et al. 2010). "
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