Chinese Medical E-ournals Database

Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition) ›› 2015, Vol. 11 ›› Issue (02): 249 -253. doi: 10.3877/cma.j.issn.1673-5250.2015.02.022

Special Issue:

Review

Research progress on relationship between paraoxonase 1 and polycystic ovary syndrome

Yujin Zhang1, Hongwei Liu1, Huai Bai2, Ping Fan2()   

  1. 1. Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
    2. Department of Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
  • Received:2014-12-01 Revised:2015-02-10 Published:2015-04-01
  • Corresponding author: Ping Fan
  • About author:
    Corresponding author: Fan Ping, Email:

Polycystic ovarian syndrome(PCOS) is one of the most common endocrine metabolic disorders. It is often associated with obesity, insulin resistance, dyslipidemia, increased oxidative stress, systemic low-grade chronic inflammation, elevated prevalences of metabolic syndrome and type 2 diabetes, and potentially increased the risks of atherosclerosis and cardiovascular disease. Paraoxonase (PON) 1 is one of high-density lipoprotein(HDL)-associated antioxidant enzymes. It possesses antioxidant, anti-inflammatory and anti-atherogenic properties. In this article, we will summarize the research progress on the genetic variations, enzyme activities and physiological functions of PON1 and their relationship to PCOS.

[1]
Li R, Zhang Q, Yang D, et al. Prevalence of polycystic ovary syndrome in women in china: a large community-based study[J]. Hum Reprod, 2013, 28(9):2562–2569.
[2]
The Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome[J]. Fertil Steril, 2004, 81(1):19–25.
[3]
Murri M, Luque-Ramirez M, Insenser M, et al. Circulating markers of oxidative stress and polycystic ovary syndrome(PCOS): a systematic review and meta-analysis[J]. Hum Reprod Update, 2013,19(3):268–288.
[4]
Zhang J, Fan P, Liu H, et al. Apolipoprotein A-I and B levels, dyslipidemia and metabolic syndrome in south-west chinese women with PCOS[J]. Hum Reprod, 2012,27(8):2484–2493.
[5]
Lim SS, Davies MJ, Norman RJ, et al. Overweight, obesity and central obesity in women with polycystic ovary syndrome: a systematic review and meta-analysis[J]. Hum Reprod Update,2012,18(6):618–637.
[6]
de Groot PC, Dekkers OM, Romijn JA, et al. PCOS, coronary heart disease, stroke and the influence of obesity: a systematic review and meta-analysis[J]. Hum Reprod Update, 2011,17(4):495–500.
[7]
Moran LJ, Misso ML, Wild RA, et al. Impaired glucose tolerance, type 2 diabetes and metabolic syndrome in polycystic ovary syndrome: a systematic review and meta-analysis[J]. Hum Reprod Update, 2010, 16(4):347–363.
[8]
Precourt LP, Amre D, Denis MC, et al. The three-gene paraoxonase family: physiologic roles, actions and regulation[J]. Atherosclerosis, 2011,214(1):20–36.
[9]
Perla-Kajan J, Jakubowski H.Paraoxonase 1 and homocysteine metabolism[J].Amino acids,2012, 43(4):1405–1417.
[10]
Camps J, Marsillach J, Joven J. The paraoxonases: role in human diseases and methodological difficulties in measurement[J]. Crit Rev Clin Lab Sci, 2009, 46(2):83–106.
[11]
Wang Y, Liu H, Fan P, et al. Evidence for association between paraoxonase 1 gene polymorphisms and polycystic ovarian syndrome in southwest chinese women[J]. Eur J Endocrinol, 2012, 166(5):877–885.
[12]
Primo-Parmo SL, Sorenson RC, Teiber J, et al. The human serum paraoxonase/arylesterase gene (PON1) is one member of a multigene family[J]. Genomics, 1996, 33(3):498–507.
[13]
Rainwater DL, Rutherford S, Dyer TD, et al. Determinants of variation in human serum paraoxonase activity[J].Heredity, 2009, 102(2):147–154.
[14]
Billecke S, Draganov D, Counsell R, et al. Human serum paraoxonase (PON1) isozymes Q and R hydrolyze lactones and cyclic carbonate esters[J]. Drug Metab Dispos, 2000, 28(11):1335–1342.
[15]
Davies HG, Richter RJ, Keifer M, et al. The effect of the human serum paraoxonase polymorphism is reversed with diazoxon, soman and sarin [J]. Nat Genet, 1996, 14(3):334–336.
[16]
Mackness B, Mackness MI, Arrol S, et al. Effect of the human serum paraoxonase 55 and 192 genetic polymorphisms on the protection by high density lipoprotein against low density lipoprotein oxidative modification[J]. FEBS Lett,1998, 423(1):57–60.
[17]
Wang M, Lang X, Zou L, et al. Four genetic polymorphisms of paraoxonase gene and risk of coronary heart disease: a meta-analysis based on 88 case-control studies[J].Atherosclerosis,2011,214(2):377–385.
[18]
Brophy VH, Jampsa RL, Clendenning JB,et al.Effects of 5' regulatory-region polymorphisms on paraoxonase-gene(PON1) expression[J]. Am J Hum Genet,2001,68(6):1428–1436.
[19]
Leviev I, Deakin S, James RW. Decreased stability of the M54 isoform of paraoxonase as a contributory factor to variations in human serum paraoxonase concentrations[J]. J Lipid Res, 2001, 42(4):528–535.
[20]
Deakin SP, James RW. Genetic and environmental factors modulating serum concentrations and activities of the antioxidant enzyme paraoxonase-1[J]. Clin Sci (Lond), 2004,107(5):435–447.
[21]
Khersonsky O,Tawfik DS. The histidine 115-histidine 134 dyad mediates the lactonase activity of mammalian serum paraoxonases[J]. J Biol Chem, 2006, 281(11):7649–7656.
[22]
Khersonsky O,Tawfik DS. Structure-reactivity studies of serum paraoxonase PON1 suggest that its native activity is lactonase[J]. Biochemistry, 2005, 44(16):6371–6382.
[23]
Aharoni A, Gaidukov L, Khersonsky O, et al. The"evolvability" of promiscuous protein functions[J]. Nat Genet, 2005, 37(1):73–76.
[24]
Khersonsky O, Roodveldt C, Tawfik DS. Enzyme promiscuity: evolutionary and mechanistic aspects[J]. Curr Opin Chem Biol,2006,10(5):498–508.
[25]
Rosenblat M,Gaidukov L,Khersonsky O,et al.The catalytic histidine dyad of high density lipoprotein-associated serum paraoxonase-1(PON1) is essential for PON1-mediated inhibition of low density lipoprotein oxidation and stimulation of macrophage cholesterol efflux[J]. J Biol Chem,2006, 281(11):7657–7665.
[26]
Rosenblat M, Vaya J, Shih D,et al.Paraoxonase 1(PON1) enhances HDL-mediated macrophage cholesterol efflux via the ABCA1 transporter in association with increased HDL binding to the cells: a possible role for lysophosphatidylcholine[J]. Atherosclerosis, 2005,179(1):69–77.
[27]
Xanthoulea S, Curfs DM, Hofker MH, et al. Nuclear factor kappa B signaling in macrophage function and atherogenesis[J]. Curr Opin Lipidol, 2005,16(5):536–542.
[28]
Navab M, Ananthramaiah GM, Reddy ST, et al. The oxidation hypothesis of atherogenesis: the role of oxidized phospholipids and HDL[J]. J Lipid Res, 2004, 45(6):993–1007.
[29]
Mackness B, Hine D, Liu Y, et al. Paraoxonase-1 inhibits oxidised LDL-induced MCP-1 production by endothelial cells[J]. Biochem Biophys Res Commun, 2004, 318(3):680–683.
[30]
Ng DS, Chu T, Esposito B, et al. Paraoxonase-1 deficiency in mice predisposes to vascular inflammation, oxidative stress, and thrombogenicity in the absence of hyperlipidemia[J]. Cardiovasc Pathol, 2008, 17(4):226–232.
[31]
Tward A, Xia YR, Wang XP,et al. Decreased atherosclerotic lesion formation in human serum paraoxonase transgenic mice[J]. Circulation, 2002, 106(4):484–490.
[32]
Duleba AJ, Dokras A. Is pcos an inflammatory process? [J]. Fertil Steril, 2012, 97(1):7–12.
[33]
Meyer ML, Malek AM, Wild RA, et al. Carotid artery intima-media thickness in polycystic ovary syndrome: a systematic review and meta-analysis[J]. Hum Reprod Update, 2012, 18(2):112–126.
[34]
Toulis KA, Goulis DG, Mintziori G,et al. Meta-analysis of cardiovascular disease risk markers in women with polycystic ovary syndrome[J]. Hum Reprod Update, 2011, 17(6):741–760.
[35]
Evans JL, Maddux BA, Goldfine ID. The molecular basis for oxidative stress-induced insulin resistance[J]. Antioxid Redox Signal, 2005, 7(7-8):1040–1052.
[36]
Rzepczynska IJ, Foyouzi N, Piotrowski PC,et al. Antioxidants induce apoptosis of rat ovarian theca-interstitial cells[J]. Biol Reprod, 2011, 84(1):162–166.
[37]
Kodaman PH, Duleba AJ. Statins in the treatment of polycystic ovary syndrome[J]. Semin Reprod Med, 2008, 26(1):127–138.
[38]
Soyman Z, Noyan V, Tulmac M, et al. Serum paraoxonase 1 activity, asymmetric dimethylarginine levels, and brachial artery flow-mediated dilatation in women with polycystic ovary syndrome[J]. Fertil Steril, 2011, 95(3):1067–1072.
[39]
Mohamadin AM, Habib FA, Elahi TF. Serum paraoxonase 1 activity and oxidant/antioxidant status in saudi women with polycystic ovary syndrome[J]. Pathophysiology, 2010, 17(3):189–196.
[40]
Fenkci IV, Serteser M, Fenkci S, et al. Paraoxonase levels in women with polycystic ovary syndrome[J]. J Reprod Med, 2007, 52(10):879–883.
[41]
Dursun P, Demirtas E, Bayrak A,et al. Decreased serum paraoxonase 1 (PON1) activity: an additional risk factor for atherosclerotic heart disease in patients with PCOS? [J]. Hum Reprod, 2006, 21(1):104–108.
[42]
Torun AN, Vural M, Cece H, et al. Paraoxonase-1 is not affected in polycystic ovary syndrome without metabolic syndrome and insulin resistance, but oxidative stress is altered[J]. Gynecol Endocrinol, 2011, 27(12):988–992.
[43]
San Millan JL, Alvarez-Blasco F, Luque-Ramirez M,et al. The PON1-108C/T polymorphism, and not the polycystic ovary syndrome, is an important determinant of reduced serum paraoxonase activity in premenopausal women[J]. Hum Reprod, 2006, 21(12):3157–3161.
[44]
Bayrak T, Dursun P, Bayrak A,et al. Paraoxonase lactonase activity (PON-HTLase), asymmetric dimethylarginine (ADMA) and platelet activating factor-acetylhydrolase (PAF-AH) activity in non-obese women with PCOS[J]. Gynecol Endocrinol, 2012,28(11):874–878.
[45]
Baskol G, Aygen E, Erdem F, et al. Assessment of paraoxonase 1, xanthine oxidase and glutathione peroxidase activities, nitric oxide and thiol levels in women with polycystic ovary syndrome[J]. Acta Obstet Gynecol Scand, 2012, 91(3):326–330.
[46]
Martinelli N, Garcia-Heredia A, Roca H, et al. Paraoxonase-1 status in patients with hereditary hemochromatosis[J]. J Lipid Res, 2013, 54(5):1484–1492.
[47]
Marsillach J, Ferre N, Vila MC, et al. Serum paraoxonase-1 in chronic alcoholics: relationship with liver disease[J]. Clin Biochem, 2007, 40(9-10):645–650.
[48]
Huang Y, Wu Z, Riwanto M, et al. Myeloperoxidase, paraoxonase-1, and hdl form a functional ternary complex[J]. J Clin Invest, 2013, 123(9):3815–3828.
[49]
Paltoglou G, Tavernarakis G, Christopoulos P, et al. PON1-108 TT and pon1-192 RR genotypes are more frequently encountered in Greek PCOS than non-PCOS women, and are associated with hyperandrogenaemia[J]. Clin Endocrinol (Oxf), 2013, 79(2):259–266.
[50]
张凤,刘宏伟,范平,等. 多囊卵巢综合征患者对氧磷酶1基因-108C/T多态性的研究[J]. 四川大学学报:医学版,2011, 42(1):24–28.
[51]
Brophy VH, Hastings MD, Clendenning JB, et al. Polymorphisms in the human paraoxonase (PON1) promoter[J]. Pharmacogenetics, 2001, 11(1):77–84.
[52]
Camps J, Marsillach J, Joven J. Pharmacological and lifestyle factors modulating serum paraoxonase-1 activity[J]. Mini Rev Med Chem, 2009, 9(8):911–920.
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