Association of paraoxonase-1 108 C >T gene polymorphism with polycystic ovarian syndrome

Year 2025, Volume: 29 Issue: 1 , 418 - 423 , 03.03.2025

Hiba Hayder Kadhum Fadia Jasim Alizzi Qasim Sharhan Al-mayah Raid Jasim Al Timimi

https://doi.org/10.12991/jrespharm.1644613

Cited By: 1

https://izlik.org/JA54SJ56HD

Abstract

Polycystic ovarian syndrome (PCOS) is increasingly recognized as a significant health concern among
women of reproductive age, exerting its influence on the reproductive system and overall female physiology.
Paraoxonase-1 (PON1) gene polymorphism, -108 C >T in the promoter region, have been identified as factors that
influence both the stability of the enzyme and its active site. This, in turn, contributes to increase oxidative stress, a
recognized risk factor associated with PCOS. This study aimed to investigate the connection between paraoxonase-1-108
C >T gen polymorphisms with PCOS in Iraqi women in a case-control study included 40 women with PCOS and 40
women with normal cycles and no symptoms of hyperandrogenism, and no history of PCOS. Whole blood was used to
extract the DNA, and using specified sets of primers, the gene fragments corresponding to the -108 C >T were amplified
using a conventional polymerase reaction (PCR). Direct sequencing was used to carry out the genotyping and the results
showed that the age, body mass index (BMI), and comorbidities of the two groups were similar. The prevalence of
homozygous genotype (TT) of the -108 C >T was greater in PCOS women (27.5%) compared to healthy women (10%),
with a significant difference (OR= 5.04, 95%CI=1.11-22.97, p=0.037). The prevalence of the mutant allele (T) was found to
be greater in women with PCOS (56.25% versus 141.25%) compared to healthy women. This difference was nearly
statistically significant (OR=1.85, 95%CI= 0.98–3.43, p= 0.059). These results confirmed the significance of -108 C >T as a
risk factor for PCOS in Iraqi women.

Keywords

PCOS , Paraoxonase-1 , PON1 -108 C>T gene polymorphisms , PON1 (rs705397) gene polymorphisms

References

• [1] Hima HA, Miah MA, Ghosh NR, Sultana S, Akter T, Aalpona FZ, Kamrul-Hasan ABM. Nonalcoholic fatty liver disease in polycystic ovary syndrome: Result of a single center cross sectional study in Bangladesh. Bangladesh J Endocrinol Metab 2023;2:80 87. http://dx.doi.org/10.4103/bjem.bjem_10_23
• [2] Borzan V, Lerchbaum E, Missbrenner C, Heijboer AC, Goschnik M, Trummer C, Theiler-Schwetz V, Haudum C, Gumpold R, Schweighofer N, Obermayer-Pietsch B. Risk of ınsulin resistance and metabolic syndrome in women with hyperandrogenemia: A comparison between PCOS phenotypes and beyond. J Clin Med. 2021;10(4):829. https://doi.org/10.3390%2Fjcm10040829
• [3] Diamanti-Kandarakis E, Piperi C. Genetics of polycystic ovary syndrome: searching for the way out of the labyrinth. Hum Reprod Update. 2005;11(6):631-643. https://doi.org/10.1093/humupd/dmi025
• [4] Goswami B, Tayal D, Gupta N, Mallika V. Paraoxonase: A multifaceted biomolecule. Clin Chim Acta. 2009;410(1 2):1-12. https://doi.org/10.1016/j.cca.2009.09.025
• [5] 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. PON1 lactonase activity and its association with cardiovascular disease. Clin Chim Acta. 2020;500:47-53. https://doi.org/10.1016/j.cca.2019.09.016
• [6] Harel M, Aharoni A, Gaidukov L, Brumshtein B, Khersonsky O, Meged R, Dvir H, Ravelli RB, McCarthy A, Toker L, Silman I, Sussman JL, Tawfik DS. Structure and evolution of the serum paraoxonase family of detoxifying and anti-atherosclerotic enzymes. Nat Struct Mol Biol. 2004;11(5):412-419. https://doi.org/10.1038/nsmb767
• [7] Aslan M, Horoz M, Sabuncu T, Celik H, Selek S. Serum paraoxonase enzyme activity and oxidative stress in obese subjects. Pol Arch Med Wewn. 2011;121(6):181-186.
• [8] Ferretti G, Bacchetti T, Moroni C, Savino S, Liuzzi A, Balzola F, Bicchiega V. Paraoxonase activity in high-density lipoproteins: A comparison between healthy and obese females. J Clin Endocrinol Metab. 2005;90(3):1728-1733. https://doi.org/10.1210/jc.2004-0486
• [9] Bayram F, Kocer D, Ozsan M, Muhtaroglu S. Evaluation of endothelial dysfunction, lipid metabolism in women with polycystic ovary syndrome: relationship of paraoxonase 1 activity, malondialdehyde levels, low-density lipoprotein subfractions, and endothelial dysfunction. Gynecol Endocrinol. 2012;28(7):497-501. https://doi.org/10.3109/09513590.2011.569607
• [10] Dursun P, Demirtaş E, Bayrak A, Yarali H. Decreased serum paraoxonase 1 (PON1) activity: an additional risk factor for atherosclerotic heart disease in patients with PCOS? Hum Reprod. 2006;21(1):104-108. https://doi.org/10.1093/humrep/dei284
• [11] Paltoglou G, Tavernarakis G, Christopoulos P, Vlassi M, Gazouli M, Deligeoroglou E, Creatsas G, Mastorakos G. PON1-108 TT and PON1-192 RR genotypes are more frequently encountered in Greek PCOS than non-PCOS women, and are associated with hyperandrogenaemia. Clin Endocrinol (Oxf). 2013;79(2):259-266. https://doi.org/10.1111/cen.12139
• [12] Mohamed A, Rashed L, Salam RA. Effect of paraoxonase gene polymorphisms on paraoxonase levels and insulin resistance index in women with polycystic ovary syndrome. Aust J Bas Appl Sci 2009;3:3346–3351.
• [13] Rosenberg SL. The Relationship Between PCOS and Obesity: Which Comes First. Sci J Lander Coll Arts Sci. 2019; 13(1):34-40.
• [14] Zeng X, Xie YJ, Liu YT, Long SL, Mo ZC. Polycystic ovarian syndrome: Correlation between hyperandrogenism, insulin resistance and obesity. Clin Chim Acta. 2020;502:214-221. https://doi.org/10.1016/j.cca.2019.11.003
• [15] Al-Mansoori L, Al-Jaber H, Prince MS, Elrayess MA. Role of ınflammatory cytokines, growth factors and adipokines in adipogenesis and ınsulin resistance. Inflammation. 2022;45(1):31-44. https://doi.org/10.1007%2Fs10753-021-01559-z
• [16] Zhou M, Liu XH, Liu QQ, Chen M, Bai H, Jiang CY, Guan LB, Fan P. Lactonase activity and status of paraoxonase 1 and oxidative stress in neonates of women with gestational diabetes mellitus. Pediatr Res. 2021;89(5):1192-1199. https://doi.org/10.1038/s41390-020-1023-2
• [17] San Millán JL, Cortón M, Villuendas G, Sancho J, Peral B, Escobar-Morreale HF. Association of the polycystic ovary syndrome with genomic variants related to insulin resistance, type 2 diabetes mellitus, and obesity. J Clin Endocrinol Metab. 2004;89(6):2640-2646. https://doi.org/10.1210/jc.2003-031252
• [18] Leviev I, Kalix B, Brulhart Meynet MC, James RW. The paraoxonase PON1 promoter polymorphism C(-107)T is associated with increased serum glucose concentrations in non-diabetic patients. Diabetologia. 2001;44(9):1177 1183. https://doi.org/10.1007/s001250100610
• [19] Liu L, Yang J, Liu Q, Yan W, Wen Y. Risk association of polycystic ovary syndrome with paraoxonase 1 and TNF-α gene polymorphisms: a meta-analysis. Int J Clin Exp Med. 2016;9(4): 7088-7101.
• [20] Zhang Y, Liu H, He J, Xu K, Bai H, Wang Y, Zhang F, Zhang J, Cheng L, Fan P. Lactonase activity and status of paraoxonase 1 in Chinese women with polycystic ovarian syndrome. Eur J Endocrinol. 2015;172(4):391-402. https://doi.org/10.1530/eje-14-0863
• [21] Precourt LP, Amre D, Denis MC, Lavoie JC, Delvin E, Seidman E and Levy E. The three-gene paraoxonase family: physiologic roles, actions and regulation. Atherosclerosis. 2011; 214: 20-36. https://doi.org/10.1016/j.atherosclerosis.2010.08.076
• [22] Ferk P, Gersak K. Association of -108 C>T PON1 polymorphism with polycystic ovary syndrome. Biomed Rep. 2014;2(2):255-259. https://doi.org/10.3892%2Fbr.2013.214
• [23] Shan H, Luo R, Guo X, Li R, Ye Z, Peng T, Liu F, Yang Z. Abnormal endometrial receptivity and oxidative stress in polycystic ovary syndrome. Front Pharmacol. 2022;13:904942. https://doi.org/10.3389/fphar.2022.904942
• [24] Al-Shammari AH, Khudhur AQ, Abdulamir HA. Effect of intralesional levofloxacin in the treatment of cutaneous leishmaniasis. J Popul Ther Clin Pharmacol. 2023;30(1): e100. https://doi.org/10.47750/jptcp.2023.1028