PON1, also known as paraoxonase 1, is a high-density lipoprotein (HDL) associated enzyme. It has antioxidant, anti-inflammatory, and anti-apoptotic roles, and its most important enzymatic activity in association with HDL is preventing low-density lipoprotein (LDL) oxidation, thus having anti-atherogenic activity [2,6,7]. PON1 is also involved in the detoxification of organophosphate insecticides [3,8].

PON1 gene polymorphisms have been associated with various diseases. A meta-analysis showed that the PON1 L55M polymorphism might increase the risk of cancer, especially breast cancer in some stratified analyses, and also increase cancer risk in Caucasian populations and in hospital-based studies [1]. Some SNPs of the PON1 gene are associated with stroke [2]. The PON1 192Q and 55L polymorphisms may increase the risk of organophosphate toxicity, especially among Caucasian populations [3]. The polymorphism of PON1 is associated with an increased risk of liver disease, and liver disease significantly reduces PON1 activity [4]. In idiopathic inflammatory myopathies (IIM), the arylesterase and lactonase activities of PON1 are significantly lower, and the PON1 QQ genotype associates with more favorable disease outcomes [5]. A meta-analysis in Chinese population suggested a weak association between the PON1 Q192R polymorphism and coronary heart disease risk [9].

In conclusion, PON1 is crucial for maintaining HDL functionality and protecting against oxidative stress and organophosphate toxicity. Its gene polymorphisms are associated with an increased risk of various diseases such as cancer, stroke, liver disease, and organophosphate toxicity, as well as influencing disease outcomes in IIM and coronary heart disease in specific populations. The study of PON1 gene polymorphisms helps to understand disease susceptibility and progression, providing potential targets for disease prevention and treatment.

References:

1. Hu, Peizeng, Ma, Yongchen, Zhang, Lingling, Ma, Sheng. 2016. PON1 L55M polymorphism might contribute to the risk of cancer. In Panminerva medica, 59, 107-113. doi:10.23736/S0031-0808.16.03212-2. https://pubmed.ncbi.nlm.nih.gov/27309259/

2. Tajbakhsh, Amir, Rezaee, Mehdi, Rivandi, Mahdi, Afzaljavan, Fahimeh, Pasdar, Alireza. 2017. Paraoxonase 1 (PON1) and stroke; the dilemma of genetic variation. In Clinical biochemistry, 50, 1298-1305. doi:10.1016/j.clinbiochem.2017.08.001. https://pubmed.ncbi.nlm.nih.gov/28779954/

3. You, Tian, Lv, Jingyu, Zhou, Liping. 2013. PON1 Q192R and L55M polymorphisms and organophosphate toxicity risk: a meta-analysis. In DNA and cell biology, 32, 252-9. doi:10.1089/dna.2012.1961. https://pubmed.ncbi.nlm.nih.gov/23590198/

4. Salari, Nader, Kazeminia, Mohsen, Mansouri, Kamran, Hosseinian-Far, Amin, Mohammadi, Masoud. 2021. The Activity and Polymorphism of the PON1 in Patients with Chronic Liver Disease: a Systematic Review and Meta-analysis. In Journal of gastrointestinal cancer, 53, 745-755. doi:10.1007/s12029-021-00699-7. https://pubmed.ncbi.nlm.nih.gov/34467517/

5. Bae, Sangmee Sharon, Shahbazian, Ani, Wang, Jennifer, Reddy, Srinivasa T, Charles-Schoeman, Christina. . Abnormal paraoxonase-1 (PON1) enzyme activity in idiopathic inflammatory myopathies. In Rheumatology (Oxford, England), 61, 2512-2523. doi:10.1093/rheumatology/keab795. https://pubmed.ncbi.nlm.nih.gov/34698804/

6. Mahrooz, Abdolkarim. 2024. Pleiotropic functions and clinical importance of circulating HDL-PON1 complex. In Advances in clinical chemistry, 121, 132-171. doi:10.1016/bs.acc.2024.04.003. https://pubmed.ncbi.nlm.nih.gov/38797541/

7. Marsillach, Judit, Richter, Rebecca J, Costa, Lucio G, Furlong, Clement E. . Paraoxonase-1 (PON1) Status Analysis Using Non-Organophosphate Substrates. In Current protocols, 1, e25. doi:10.1002/cpz1.25. https://pubmed.ncbi.nlm.nih.gov/33484495/

8. Costa, Lucio G, Giordano, Gennaro, Cole, Toby B, Marsillach, Judit, Furlong, Clement E. 2012. Paraoxonase 1 (PON1) as a genetic determinant of susceptibility to organophosphate toxicity. In Toxicology, 307, 115-22. doi:10.1016/j.tox.2012.07.011. https://pubmed.ncbi.nlm.nih.gov/22884923/

9. Zhang, Zhen, Ou, Junke, Cai, Peiling, Niu, Bei, Li, Jian. . Association between the PON1 Q192R polymorphism and coronary heart disease in Chinese: A meta-analysis. In Medicine, 97, e11151. doi:10.1097/MD.0000000000011151. https://pubmed.ncbi.nlm.nih.gov/29952962/