Toxoplasma gondii Seropositivity Interacts with Catechol- O-methyltransferase Val105/158Met Variation Increasing the Risk of Schizophrenia

Genes (Basel). 2022 Jun 18;13(6):1088. doi: 10.3390/genes13061088.


Schizophrenia is a heterogeneous and severe psychotic disorder. Epidemiological findings have suggested that the exposure to infectious agents such as Toxoplasma gondii (T. gondii) is associated with an increased risk for schizophrenia. On the other hand, there is evidence involving the catechol-O-methyltransferase (COMT) Val105/158Met polymorphism in the aetiology of schizophrenia since it alters the dopamine metabolism. A case−control study of 141 patients and 142 controls was conducted to analyse the polymorphism, the prevalence of anti-T. gondii IgG, and their interaction on the risk for schizophrenia. IgG were detected by ELISA, and genotyping was performed with TaqMan Real-Time PCR. Although no association was found between any COMT genotype and schizophrenia, we found a significant association between T. gondii seropositivity and the disorder (χ2 = 11.71; p-value < 0.001). Furthermore, the risk for schizophrenia conferred by T. gondii was modified by the COMT genotype, with those who had been exposed to the infection showing a different risk compared to that of nonexposed ones depending on the COMT genotype (χ2 for the interaction = 7.28, p-value = 0.007). This study provides evidence that the COMT genotype modifies the risk for schizophrenia conferred by T. gondii infection, with it being higher in those individuals with the Met/Met phenotype, intermediate in heterozygous, and lower in those with the Val/Val phenotype.

Keywords: COMT; Toxoplasma gondii; case–control study; gene–environment interaction; infectious agents; schizophrenia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Catechol O-Methyltransferase* / genetics
  • Humans
  • Immunoglobulin G
  • Schizophrenia* / genetics
  • Toxoplasma
  • Toxoplasmosis* / genetics


  • Immunoglobulin G
  • COMT protein, human
  • Catechol O-Methyltransferase

Grant support

This research was funded by the Andalusian Secretary of Innovation and Science (Junta de Andalucía; Excellence grant no. P06-CTS-01686), the Spanish Ministry of Health via the Instituto de Salud Carlos III (grant nos.: FIS PS09/01671, PI13/01967, PI18/00467) and Programa Operativo FEDER 2018, Ref. B-CTS-361-UGR18.