Genotype-phenotype Analysis of Paraoxonase 1 in Schizophrenic Patients Treated with Atypical Antipsychotics

Overview

Journal Clin Psychopharmacol Neurosci

Specialty Psychiatry

Date 2018 Feb 6

PMID 29397664

Citations 3

Authors

Denis Paval

Bogdan Nemes

Razvan L Rusu

Eleonora Dronca

Affiliations

Soon will be listed here.

Abstract

Objective: Recent studies suggest a possible involvement of low paraoxonase 1 (PON1) enzyme activities in the association between schizophrenia, treatment with atypical antipsychotics and increased cardiovascular (CVD) risk. In the present study, we aimed at investigating the PON1 status in a group of schizophrenic patients treated with either olanzapine or other antipsychotic, as compared to a group of healthy control participants.

Methods: We assessed the arylesterase (AREase) and paraoxonase (POase) activities of PON1, as well as three common polymorphisms of gene (Q192R, L55M, -108C＞T).

Results: We found significantly lower (-13.3%) AREase activity in schizophrenic patients, along with significantly lower (-18.2%) POase activity in olanzapine-treated patients with QQ genotype. Furthermore, we found a significant difference between groups in L55M polymorphism distribution, whereas Q192R and -108C＞T polymorphisms distributions were similar.

Conclusion: We identified the olanzapine-treated patients with QQ genotype as having the lowest PON1 (POase) activity, providing a possible way of identifying schizophrenic patients exposed to the greatest risk of CVD.

Citing Articles

Paraoxonase/Arylesterase Activity of Serum Paraoxonase-1 and Schizophrenia: A Systematic Review and Meta-Analysis.

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Developing a Sensitive Platform to Measure 5-Methyltetrahydrofolate in Subjects with MTHFR and PON1 Gene Polymorphisms.

Lu M, Ku W, Syifa N, Hu S, Chou C, Wu Y Nutrients. 2022; 14(16).

PMID: 36014826 PMC: 9412631. DOI: 10.3390/nu14163320.

Why Should Psychiatrists and Neuroscientists Worry about Paraoxonase 1?.

Moreira E, Boll K, Correia D, Soares J, Rigobello C, Maes M Curr Neuropharmacol. 2018; 17(11):1004-1020.

PMID: 30592255 PMC: 7052826. DOI: 10.2174/1570159X17666181227164947.

References

Eckerson H, Wyte C, La Du B . The human serum paraoxonase/arylesterase polymorphism. Am J Hum Genet. 1983; 35(6):1126-38. PMC: 1685985. View

Gunes M, Camkurt M, Bulut M, Demir S, Okan Ibiloglu A, Cemal Kaya M . Evaluation of Paraoxonase, Arylesterase and Malondialdehyde Levels in Schizophrenia Patients Taking Typical, Atypical and Combined Antipsychotic Treatment. Clin Psychopharmacol Neurosci. 2016; 14(4):345-350. PMC: 5083945. DOI: 10.9758/cpn.2016.14.4.345. View

Haro J, Salvador-Carulla L . The SOHO (Schizophrenia Outpatient Health Outcome) study: implications for the treatment of schizophrenia. CNS Drugs. 2006; 20(4):293-301. DOI: 10.2165/00023210-200620040-00003. View

Kucukali C, Aydin M, Ozkok E, Orhan N, Cakir U, Kilic G . Paraoxonase-1 55/192 genotypes in schizophrenic patients and their relatives in Turkish population. Psychiatr Genet. 2008; 18(6):289-94. DOI: 10.1097/YPG.0b013e3283060f94. View

Gan K, Smolen A, Eckerson H, La Du B . Purification of human serum paraoxonase/arylesterase. Evidence for one esterase catalyzing both activities. Drug Metab Dispos. 1991; 19(1):100-6. View

Brophy V, Jampsa R, Clendenning J, McKinstry L, Jarvik G, Furlong C . Effects of 5' regulatory-region polymorphisms on paraoxonase-gene (PON1) expression. Am J Hum Genet. 2001; 68(6):1428-36. PMC: 1226129. DOI: 10.1086/320600. View

Mackness B, Mackness M, Arrol S, Turkie W, Julier K, Abuasha B . Serum paraoxonase (PON1) 55 and 192 polymorphism and paraoxonase activity and concentration in non-insulin dependent diabetes mellitus. Atherosclerosis. 1998; 139(2):341-9. DOI: 10.1016/s0021-9150(98)00095-1. View

Sarandol A, Kirli S, Akkaya C, Ocak N, Eroz E, Sarandol E . Coronary artery disease risk factors in patients with schizophrenia: effects of short term antipsychotic treatment. J Psychopharmacol. 2007; 21(8):857-63. DOI: 10.1177/0269881107077609. View

Andreasen N, Pressler M, Nopoulos P, Miller D, Ho B . Antipsychotic dose equivalents and dose-years: a standardized method for comparing exposure to different drugs. Biol Psychiatry. 2009; 67(3):255-62. PMC: 3677042. DOI: 10.1016/j.biopsych.2009.08.040. View

10.

Melkersson K, Dahl M . Adverse metabolic effects associated with atypical antipsychotics: literature review and clinical implications. Drugs. 2004; 64(7):701-23. DOI: 10.2165/00003495-200464070-00003. View

11.

Precourt L, Amre D, Denis M, Lavoie J, Delvin E, Seidman E . The three-gene paraoxonase family: physiologic roles, actions and regulation. Atherosclerosis. 2010; 214(1):20-36. DOI: 10.1016/j.atherosclerosis.2010.08.076. View

12.

Gupta N, Singh S, Maturu V, Sharma Y, Gill K . Paraoxonase 1 (PON1) polymorphisms, haplotypes and activity in predicting cad risk in North-West Indian Punjabis. PLoS One. 2011; 6(5):e17805. PMC: 3101202. DOI: 10.1371/journal.pone.0017805. View

13.

Yogaratnam J, Biswas N, Vadivel R, Jacob R . Metabolic complications of schizophrenia and antipsychotic medications--an updated review. East Asian Arch Psychiatry. 2013; 23(1):21-8. View

14.

Richter R, Jarvik G, Furlong C . Determination of paraoxonase 1 status without the use of toxic organophosphate substrates. Circ Cardiovasc Genet. 2009; 1(2):147-52. PMC: 3035628. DOI: 10.1161/CIRCGENETICS.108.811638. View

15.

Unsal C, Albayrak Y, Albayrak N, Kuloglu M, Hashimoto K . Reduced serum paraoxonase 1 (PON1) activity in patients with schizophrenia treated with olanzapine but not quetiapine. Neuropsychiatr Dis Treat. 2013; 9:1545-52. PMC: 3798239. DOI: 10.2147/NDT.S52463. View

16.

Mackness M, Mackness B . Human paraoxonase-1 (PON1): Gene structure and expression, promiscuous activities and multiple physiological roles. Gene. 2015; 567(1):12-21. PMC: 4458450. DOI: 10.1016/j.gene.2015.04.088. View

17.

Noto C, Ota V, Gadelha A, Noto M, Barbosa D, Bonifacio K . Oxidative stress in drug naïve first episode psychosis and antioxidant effects of risperidone. J Psychiatr Res. 2015; 68:210-6. DOI: 10.1016/j.jpsychires.2015.07.003. View

18.

Hennekens C, Hennekens A, Hollar D, Casey D . Schizophrenia and increased risks of cardiovascular disease. Am Heart J. 2005; 150(6):1115-21. DOI: 10.1016/j.ahj.2005.02.007. View

19.

Costa L, Vitalone A, Cole T, Furlong C . Modulation of paraoxonase (PON1) activity. Biochem Pharmacol. 2005; 69(4):541-50. DOI: 10.1016/j.bcp.2004.08.027. View

20.

Bruijnzeel D, Suryadevara U, Tandon R . Antipsychotic treatment of schizophrenia: an update. Asian J Psychiatr. 2014; 11:3-7. DOI: 10.1016/j.ajp.2014.08.002. View