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Polymorphisms in PLA2G4A and PLA2G6 genes and plasma lipid and glucose concentrations in schizophrenia patients

INTRODUCTION: The release of arachidonic acid (20:4n-6, ARA) from membrane phospholipids via the activation of phospholipase A2 (PLA2) enzymes is thought to be involved in dopaminergic signaling and insulin secretion. Altered dopaminergic neurotransmission, disturbances of glucose and lipid metabolism and increased PLA2 activity are repeatedly observed in schizophrenia patients. The rs10798059 (BanI) and rs4375 polymorphisms in (PLA2)G4A and PLA2G6 genes have proved to be relevant in etiology and clinical expression of schizophrenia, as measured by the Positive and Negative Syndrome Scale and/or the age of disease onset. AIM: We investigated whether fasting plasma lipid and glucose concentrations might be influenced by rs10798059 (BanI) and rs4375 polymorphic variants among chronically ill Croatian schizophrenia patients. PATIENTS AND METHODS: Genotyping was performed by polymerase chain reaction/restriction fragment length polymorphism analysis for 263 patients (males/females: 139/124). RESULTS: Total cholesterol and LDL cholesterol concentrations in females and triglyceride levels in males were slightly elevated relative to the reference values, and mean body mass index values were in the overweight range in both genders. We revealed no significant association between PLA2G6 polymorphism and plasma lipid and glucose concentrations neither among male, nor among female patients, whereas the PLA2G4A polymorphism significantly contributed to plasma glucose levels in female patients only. Specifically, females carrying the PLA2G4A-G allele (PLA2G4A-GG homozygous and PLA2G4A-AG heterozygous) had lower glucose levels than PLA2G4A-AA homozygous carriers (5.5 ± 0.8 vs. 6.6 ± 2.0 ; F = 13.03, P < 0.001). The PLA2G4A genotype accounted for approximately 6% of the variability in glucose levels. CONCLUSION: BanI polymorphism in the PLA2G4A gene has significant, although weak influence on plasma glucose levels among female patients, yet it does not affect any other metabolic parameters, neither among males, nor among females. Finally, the rs4375 (PLA2G6) polymorphism does not contribute to lipid or glucose concentrations in the patient group.

glucose ; lipids ; phospholipases A2, polymorphism ; schizophrenia.

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