engleski

An association between PLA2G4A and PLA2G6 gene polymorphisms with smoking risk and illness severity in schizophrenia patients

Introduction: Hypodopaminergy in the prefrontal cortex may explain negative symptoms, cognitive deficits, as well as high smoking rate in schizophrenia patients. Evidence indicates that increased phospholipase A2 (PLA2) activity, repeatedly observed in brain and various peripheral tissues among schizophrenia individuals, could accelerate the breakdown of membrane phospholipids and contribute to a prefrontal hypodopaminergy. Data regarding the relevance of PLA2 genes in the clinical expression of schizophrenia are sparse and no studies have elucidated the associations between the PLA2 genes and nicotine dependence. We investigated the plausible relationship between the rs10798059 (BanI) and rs4375 polymorphisms in (PLA2)G4A and PLA2G6 genes and the risk for nicotine dependence among Croatian schizophrenia patients. We also examined whether these polymorphic variants alone, or in interactions with smoking status, might contribute to schizophrenia onset and scores for the Positive and Negative Syndrome Scale (PANSS) during an acute state of the illness requiring hospitalization. Methods: Genotyping was performed by polymerase chain reaction for 263 patients (males/females: 139/124) who met DSM-IV criteria for schizophrenia Results and discussion: We demonstrated three significant, yet weak effects, manifesting in a gender-specific fashion. An overrepresentation of PLA2G6-CC homozygous and CT heterozygous genotypes was detected in male nonsmokers compared to smokers (χ2=3.03, P<0.05) ; PLA2G6-CC homozygous and CT heterozygous males had about a 2.5-fold lower smoking risk than TT homozygous. Furthermore, females carrying the G allele in their PLA2G4A genotype (PLA2G4A-GG homozygous and AG heterozygous) manifested a significantly lower negative and total PANSS scores compared to AA homozygous (P<0.05 and P<0.01). Finally, we detected an intriguing PLA2G6 genotype-smoking interaction that predicted the time of illness onset among males (P<0.05) ; an earlier onset was observed for smokers PLA2G6-TT homozygous in comparison to nonsmoking TT homozygous (F=4.07, P<0.05).

age at first hospitalization ; PLA2G6 gene ; polymorphism ; schizophrenia ; smoking

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