Abstract
Although many studies have investigated the association of paraoxonase 1 (PON1) polymorphisms with coronary artery disease (CAD). However, the outcomes were not consistent and remain uncertain. Therefore, it is the need of the hour to analyze the available literature and evaluate the association of PON1 polymorphisms with the CAD. All the relevant studies published in the English language from January 1, 2000, up to September 20, 2020, were identified by searching through various electronic databases. The two researchers independently extracted the information. The data were analyzed by using the MetaGenyo program. The pooled odds ratio was used to find the associations between CAD and PON1 polymorphisms. In the final analysis, we include 10 studies regarding the association of PON1 polymorphisms (rs662 and rs854560) with CAD. Overall, the Q192R polymorphism increased the risk of CAD in the tested genetic models including the homozygote model: OR 1.35, CI 1.02–1.79; allelic model: OR 1.16, CI 1.00–1.33; dominant model: OR 1.25, CI 1.03–1.52. The L55M polymorphism does not significantly associated with CAD in all the tested genetic models including the homozygote model: OR 1.00 CI, 0.64–1.56; allelic model: OR 1.02, 95% CI 0.84–1.23; dominant model: OR 1.08, CI 0.89–1.31. Further analysis showed no publication bias exists in meta-analysis. Our findings suggested that rs662 in the coding region was significantly associated with the CAD however, rs854560 has no significant association with the disease. Nevertheless, in future, there is a need for more studies with a larger sample size which may provide a more definite conclusion.
Study Registration: PROSPERO registration number CRD42020202278
Similar content being viewed by others
References
Ahmad I, Narang R, Venkatraman A, Das N (2012) Two-and three-locus haplotypes of the paraoxonase (PON1) gene are associated with coronary artery disease in Asian Indians. Gene 506:242–247. https://doi.org/10.1016/j.gene.2012.06.031
Ashiq S, Ashiq K, Shabana S, Shahid SU, Qayyum M, Sadia H (2020) Prevalence and role of different risk factors with emphasis on genetics in development of pathophysiology of coronary artery disease (CAD). Pak Heart J 52:279–287
Birjmohun RS, Vergeer M, Stroes ES, Sandhu MS, Ricketts SL, Tanck MW, Wareham NJ, Jukema JW, Kastelein JJ, Khaw KT, Boekholdt SM (2009) Both paraoxonase-1 genotype and activity do not predict the risk of future coronary artery disease; the EPIC-Norfolk prospective population study. PLoS ONE 4:e6809. https://doi.org/10.1371/journal.pone.0006809
Bounafaa A, Berrougui H, Ghalim N, Nasser B, Bagri A, Moujahid A, Ikhlef S, Camponova P, Yamoul N, Simo OK, Essamadi A (2015) Association between Paraoxonase 1 (PON1) polymorphisms and the risk of acute coronary syndrome in a north African population. PLoS ONE 10:e0133719. https://doi.org/10.1371/journal.pone.0133719
Egger M, Smith GD, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634. https://doi.org/10.1136/bmj.315.7109.629
El-Lebedy D, Kafoury M, Abd-El Haleem D, Ibrahim A, Awadallah E, Ashmawy I (2014) Paraoxonase-1 gene Q192R and L55M polymorphisms and risk of cardiovascular disease in Egyptian patients with type 2 diabetes mellitus. J Diabetes Metab Disord 13:124. https://doi.org/10.1186/s40200-014-0125-y
Fridman O, Gariglio L, Riviere S, Porcile R, Fuchs A, Potenzoni M (2016) Paraoxonase 1 gene polymorphisms and enzyme activities in coronary artery disease and its relationship to serum lipids and glycemia. Arch Cardiol Mex 86:350–357. https://doi.org/10.1016/j.acmx.2016.08.001
Godbole C, Thaker S, Kerkar P, Nadkar M, Gogtay N, Thatte U (2020) Association of PON1 gene polymorphisms and enzymatic activity with risk of coronary artery disease. Future Cardiol. https://doi.org/10.2217/fca-2020-0028
Gupta N, Binu KB, Singh S, Maturu NV, Sharma YP, Bhansali A, Gill KD (2012) Low serum PON1 activity: an independent risk factor for coronary artery disease in North-West Indian type 2 diabetics. Gene 498:13–19. https://doi.org/10.1016/j.gene.2012.01.091
Hassan MA, Al-Attas OS, Hussain T, Al-Daghri NM, Alokail MS, Mohammed AK, Vinodson B (2013) The Q192R polymorphism of the paraoxonase 1 gene is a risk factor for coronary artery disease in Saudi subjects. Mol cell Biochem 380:121–128. https://doi.org/10.1007/s11010-013-1665-z
Hazar A, Dilmec F, Göz M, Koçarslan A, Aydin MS, Demirkol AH (2011) The paraoxonase 1 (PON1) gene polymorphisms in coronary artery disease in the southeastern Turkish population. Turk J Med Sci 41:895–902. https://doi.org/10.3906/sag-1009-1168
Hernández-Díaz Y, Tovilla-Zárate CA, Juárez-Rojop IE, González-Castro TB, Rodríguez-Pérez C, López-Narváez ML, Rodríguez-Pérez JM, Cámara-Álvarez JF (2016) Effects of paraoxonase 1 gene polymorphisms on heart diseases: systematic review and meta-analysis of 64 case-control studies. Medicine 95:e5298. https://doi.org/10.1097/MD.0000000000005298
Jamee Shahwan A, Abed Y, Desormais I, Magne J, Preux PM, Aboyans V, Lacroix P (2019) Epidemiology of coronary artery disease and stroke and associated risk factors in Gaza community–Palestine. PLoS ONE 14:e0211131. https://doi.org/10.1371/journal.pone.0211131
Kaman D, İlhan N, Metin K, Akbulut M, Üstündağ B (2009) A preliminary study of human paraoxonase and PON 1 L/M55–PON 1 Q/R 192 polymorphisms in Turkish patients with coronary artery disease. Cell Biochem Funct 27:88–92. https://doi.org/10.1002/cbf.1539
Kaur S, Bhatti GK, Vijayvergiya R, Singh P, Mastana SS, Tewari R, Bhatti JS (2018) Paraoxonase 1 gene polymorphisms (Q192R and L55M) are associated with coronary artery disease susceptibility in Asian Indians. Int J Diabetes Metab 21:38–47. https://doi.org/10.1159/000494508
Larifla L, Beaney KE, Foucan L, Bangou J, Michel CT, Martino J, Velayoudom-Cephise FL, Cooper JA, Humphries SE (2016) Influence of genetic risk factors on coronary heart disease occurrence in Afro-Caribbeans. Can J Cardiol 32:978–985. https://doi.org/10.1016/j.cjca.2016.01.004
Lawlor DA, Day IN, Gaunt TR, Hinks LJ, Briggs PJ, Kiessling M, Timpson N, Smith GD, Ebrahim S (2004) The association of the PON1 Q192R polymorphism with coronary heart disease: findings from the British Women’s Heart and Health cohort study and a meta-analysis. BMC Genet 5:17. https://doi.org/10.1186/1471-2156-5-17
Liu T, Zhang X, Zhang J, Liang Z, Cai W, Huang M, Yan C, Zhu Z, Han Y (2014) Association between PON1 rs662 polymorphism and coronary artery disease. Eur J Clin Nutr 68:1029–1035. https://doi.org/10.1038/ejcn.2014.105
Matam K, Khan IA, Hasan Q, Rao P (2015) Coronary artery disease and the frequencies of MTHFR and PON1 gene polymorphism studies in a varied population of Hyderabad, Telangana region in south India. J King Saud Univ Sci 27:143–150. https://doi.org/10.1016/j.jksus.2014.09.002
Mohamed RH, Mohamed RH, Karam RA, Abd El-Aziz TA (2010) The relationship between paraoxonase1-192 polymorphism and activity with coronary artery disease. Clin Biochem 43:553–558. https://doi.org/10.1016/j.clinbiochem.2009.12.015
Moreno-Godínez ME, Galarce-Sosa C, Cahua-Pablo JÁ, Rojas-García AE, Huerta-Beristain G, del Carmen A-R, Cruz M, Valladares-Salgado A, Antonio-Véjar V, Ramírez-Vargas MA, Flores-Alfaro E (2018) Genotypes of common polymorphisms in the PON1 gene associated with paraoxonase activity as cardiovascular risk factor. Arch Med Res 49:486–496. https://doi.org/10.1016/j.arcmed.2019.02.002
Munshi R, Panchal F, Chaurasia A, Rajadhyaksha G (2018) Association between paraoxonase 1 (PON1) Gene Polymorphisms and PON1 enzyme activity in Indian patients with coronary artery disease (CAD). Curr Pharmacogenom Pers Med 16:219–229. https://doi.org/10.2174/1875692117666181227112119
Murillo-González FE, Ponce-Ruiz N, Rojas-García AE, Rothenberg SJ, Bernal-Hernández YY, Cerda-Flores RM, Mackness M, Barrón-Vivanco BS, González-Arias CA, Ponce-Gallegos J, Medina-Díaz IM (2020) PON1 lactonase activity and its association with cardiovascular disease. Clin Chim Acta 500:47–53. https://doi.org/10.1016/j.cca.2019.09.016
Sekhri T, Kanwar RS, Wilfred R, Chugh P, Chhillar M, Aggarwal R, Sharma YK, Sethi J, Sundriyal J, Bhadra K, Singh S (2014) Prevalence of risk factors for coronary artery disease in an urban Indian population. BMJ Open 4:e005346. https://doi.org/10.1136/bmjopen-2014-005346
Shabana N, Ashiq S, Ijaz A, Khalid F, ul Saadat I, Khan K, Sarwar S, Shahid SU (2018) Genetic risk score (GRS) constructed from polymorphisms in the PON1, IL-6, ITGB3, and ALDH2 genes is associated with the risk of coronary artery disease in Pakistani subjects. Lipids Health Dis 17:224. https://doi.org/10.1186/s12944-018-0874-6
Shahid SU, Shabana NA, Rehman A, Humphries S (2018) GWAS implicated risk variants in different genes contribute additively to increase the risk of coronary artery disease (CAD) in the Pakistani subjects. Lipids Health Dis 17:89. https://doi.org/10.1186/s12944-018-0736-2
Shahsavari G, Nouryazdan N, Adibhesami G, Birjandi M (2020) Genetic associations and serum paraoxonase levels with atherosclerosis in western Iranian patients. Mol Biol Rep 47:5137–5144. https://doi.org/10.1007/s11033-020-05585-2
Szpakowicz A, Pepinski W, Waszkiewicz E, Maciorkowska D, Skawronska M, Niemcunowicz-Janica A, Dobrzycki S, Musial WJ, Kaminski KA (2016) The influence of renal function on the association of rs854560 polymorphism of paraoxonase 1 gene with long-term prognosis in patients after myocardial infarction. Heart Vessels 31:15–22. https://doi.org/10.1007/s00380-014-0574-8
Taşkıran P, Çam SF, Şekuri C, Tüzün N, Alioğlu E, Altıntaş N, Berdeli A (2009) The relationship between paraoxanase gene Leu-Met (55) and Gln-Arg (192) polymorphisms and coronary artery disease. Turk Kardiyol Dern Ars 37:473–478
Wang Y, Chen Y, Zhai X, Zhao X, Guo R, Yu B, Zhang W, **e J (2018) Genetic variants of the paraoxonase 1 gene and risk of coronary heart disease and stroke in the Chinese population: a meta-analysis. Int J Clin Exp Med 11:3010–3022
Zeng Q, Zeng J (2019) A meta-analysis on relationship between paraoxonase 1 polymorphisms and atherosclerotic cardiovascular diseases. Life Sci 232:116646. https://doi.org/10.1016/j.lfs.2019.116646
Zhang Z, Ou J, Cai P, Niu B, Li J (2018) Association between the PON1 Q192R polymorphism and coronary heart disease in Chinese: a meta-analysis. Medicine 97:e11151. https://doi.org/10.1097/MD.0000000000011151
Funding
Not Applicable.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflicts of interests
The authors declare that they have no conflict of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Ashiq, S., Ashiq, K. The Role of Paraoxonase 1 (PON1) Gene Polymorphisms in Coronary Artery Disease: A Systematic Review and Meta-Analysis. Biochem Genet 59, 919–939 (2021). https://doi.org/10.1007/s10528-021-10043-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10528-021-10043-0