Association between the COX-2 rs689466 polymorphism and antipsychotic treatment: Impact on HDL cholesterol changes in clozapine-treated psychosis patients.

Several studies have shown antipsychotic effects of the selective cyclooxygenase-2 (COX-2) inhibitor celecoxib as an add-on treatment to antipsychotic treatment. The functional rs689466 (A/G) polymorphism in the gene encoding COX-2 (also known as the prostaglandin-endoperoxide synthase 2 gene) has been correlated with schizophrenia risk and the niacin skin flush response among chronic patients under antipsychotic treatment. Here, we investigated whether this polymorphism was associated with antipsychotic treatment in a group of total psychosis patients (N = 186), as well as a subgroup of patients treated with clozapine (N = 74). Antipsychotic-naïve first-episode patients and non-adherent chronic psychosis patients were genotyped by polymerase chain reaction/restriction fragment length polymorphism analysis. At baseline and after 8 weeks of treatment with various antipsychotic medications, we assessed the patients' Positive and Negative Syndrome Scale (PANSS) scores, factors, and metabolic syndrome-related parameters, including fasting plasma lipid and glucose levels and body mass index. In the total patient group, the COX-2 polymorphism was not associated with PANSS psychopathology scores or metabolic parameters. However, in the subgroup of patients treated with clozapine, the COX-2 polymorphism was associated with changes in plasma HDL cholesterol. Specifically, compared to patients homozygous for the A allele, the subgroup of patients treated with clozapine and positive for the G allele (i.e., GG or AG genotype) exhibited significantly higher increases in HDL cholesterol levels. The COX-2 polymorphism had a moderate effect size but made a relatively weak contribution to variations in the HDL cholesterol level (∼9.6 %).