Sergej Nadalin , Ivan Ljoka , Aleksandar Savić , Ante Silić , Vjekoslav Peitl , Dalibor Karlović , Maja Vilibić , Lena Zatković , Alena Buretić-Tomljanović
{"title":"COX-2 rs689466多态性与抗精神病治疗的关系:对氯氮平治疗精神病患者HDL胆固醇变化的影响","authors":"Sergej Nadalin , Ivan Ljoka , Aleksandar Savić , Ante Silić , Vjekoslav Peitl , Dalibor Karlović , Maja Vilibić , Lena Zatković , Alena Buretić-Tomljanović","doi":"10.1016/j.plefa.2025.102665","DOIUrl":null,"url":null,"abstract":"<div><div>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 (<em>N</em> = 186), as well as a subgroup of patients treated with clozapine (<em>N</em> = 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 %).</div></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"204 ","pages":"Article 102665"},"PeriodicalIF":3.2000,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Association between the COX-2 rs689466 polymorphism and antipsychotic treatment: Impact on HDL cholesterol changes in clozapine-treated psychosis patients\",\"authors\":\"Sergej Nadalin , Ivan Ljoka , Aleksandar Savić , Ante Silić , Vjekoslav Peitl , Dalibor Karlović , Maja Vilibić , Lena Zatković , Alena Buretić-Tomljanović\",\"doi\":\"10.1016/j.plefa.2025.102665\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>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 (<em>N</em> = 186), as well as a subgroup of patients treated with clozapine (<em>N</em> = 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 %).</div></div>\",\"PeriodicalId\":94179,\"journal\":{\"name\":\"Prostaglandins, leukotrienes, and essential fatty acids\",\"volume\":\"204 \",\"pages\":\"Article 102665\"},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2025-01-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Prostaglandins, leukotrienes, and essential fatty acids\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S095232782500002X\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Prostaglandins, leukotrienes, and essential fatty acids","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S095232782500002X","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
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 %).