PLA2G10 and Schizophrenia

This summary reviews the association between PLA2G10 (HGNC:9029) and schizophrenia (MONDO_0005090). Two independent case‑control studies were performed to assess allelic associations of several phospholipase‑A2 genes, including PLA2G10, with schizophrenia. The overall evidence has been derived from relatively modest cohorts and does not clearly support a pathogenic role for PLA2G10 in schizophrenia (PMID:15318030). The studies examined multiple gene polymorphisms, where PLA2G10 was one of the targets among other phospholipase‑A2 family members.

In the first study, a case‑control analysis involving 240 schizophrenic patients and 312 healthy controls evaluated several phospholipase‑A2 gene polymorphisms. Although the investigation found a significant allelic and genotypic association with an iPLA2 gene polymorphism, the distribution for sPLA2 gene polymorphisms, which includes PLA2G10, showed no significant difference between groups (PMID:15318030). The lack of association for PLA2G10 was noted despite the comprehensive analysis of the gene family, thereby questioning its role as a susceptibility factor in schizophrenia.

A subsequent study further explored the association of phospholipase‑A2 genes with schizophrenia in a combined cohort of 328 patients and their parents. This investigation, which specifically highlighted PLA2G10 alongside KAT5, reported marginally significant findings that did not survive correction for multiple testing (PMID:11353443). Detailed segregation analysis of allelic variants failed to demonstrate a significant genetic effect for PLA2G10 in the etiology of schizophrenia. Furthermore, no additional affected relatives with segregating PLA2G10 variants were reported in these studies.

The genetic evidence is supported by the identification of variants in PLA2G10; for example, the coding variant c.112C>T (p.Arg38Cys) has been reported in other contexts. However, the presence of this variant has not been correlated with phenotypic severity or consistent disease manifestation in schizophrenia cohorts. This variant, while valid by HGVS nomenclature, does not influence the overall genetic association when considered alongside the negative association findings from the case‑control studies.

Functional or experimental studies directly examining the consequence of PLA2G10 variation in schizophrenia are lacking. Although functional assays have been conducted for PLA2G10 in the context of coronary artery disorder and other inflammatory conditions, no investigations have provided compelling evidence that PLA2G10 dysfunction contributes to the pathophysiology of schizophrenia. This gap in experimental concordance further diminishes the likelihood of a clinically actionable association for diagnostic decision-making in schizophrenia.

In conclusion, the current body of genetic evidence, including two independent case‑control studies involving 240 (PMID:15318030) and 328 families (PMID:11353443) respectively, does not support a significant association between PLA2G10 and schizophrenia. The absence of functional evidence specific to this phenotype and the overall negative or marginal statistical findings result in a disputed classification. Key take‑home: Without robust genetic or functional data, PLA2G10 currently lacks clinical utility as a diagnostic marker for schizophrenia.

References

• Psychiatric genetics • 2004 • Allelic association analysis of phospholipase A2 genes with schizophrenia PMID:15318030
• American journal of medical genetics • 2001 • Lack of association between schizophrenia and the phospholipase-A(2) genes cPLA2 and sPLA2 PMID:11353443

Evidence Based Scoring (AI generated)