Does the presenilin 2 gene predispose to schizophrenia?

Area of Science:

• Neurogenetics
• Molecular Psychiatry
• Human Genetics

Background:

• Presenilins are crucial proteins in cellular signaling pathways, including Notch, ErbB4, and Wnt.
• The presenilin 2 (PSEN2) gene's location near a translocation associated with schizophrenia suggests a potential role in the disorder's pathogenesis.

Purpose of the Study:

• To investigate the association between functional single nucleotide polymorphisms (SNPs) in the PSEN2 gene and schizophrenia risk.
• To explore the relationship between PSEN2 gene expression, genotypes, and clinical phenotypes in schizophrenia patients.

Main Methods:

• Genotyping of five functional PSEN2 SNPs (rs1295645, rs11405, rs6759, rs1046240, rs8383) in 410 schizophrenia patients and 355 controls.
• Analysis of PSEN2 mRNA expression levels in peripheral leukocytes.
• Correlation analysis between genotypes, gene expression, and Positive and Negative Syndrome Scale (PANSS) scores.

Main Results:

• A significant association was found between the rs1295645 SNP and an increased risk of schizophrenia (corrected p=0.045, OR=1.32).
• The T-C-T-T-T haplotype of PSEN2 showed a strong association with elevated schizophrenia risk (p=1.8x10(-5), OR=3.37).
• Lower PSEN2 mRNA levels were observed in patients compared to controls, correlating with specific genotypes.

Conclusions:

• The PSEN2 gene is a potential novel candidate gene contributing to the development of schizophrenia.
• Specific PSEN2 genetic variations and altered gene expression may be implicated in certain psychotic symptoms.
• Further replication studies in larger populations are necessary to confirm these findings.