Top

Journal of Endocrinological Investigation

Published in:

01-11-2018 | Original Article

Association of PON1 gene polymorphisms with polycystic ovarian syndrome risk: a meta-analysis of case–control studies

Authors: D. Liao, H. Yu, L. Han, C. Zhong, X. Ran, D. Wang, L. Mo

Published in: Journal of Endocrinological Investigation | Issue 11/2018

Abstract

Purpose

Evidences showed that paraoxonase 1 (PON1) gene polymorphism has an impact on women’s susceptibility to polycystic ovarian syndrome (PCOS) by influencing the expression and activity of PON1. However, the effects of three PON1 polymorphisms (− 108 C>T, L55M and Q192R) on the incidence of PCOS have generated inconsistent results. Here, we conducted a meta-analysis to investigate the association between PON1 polymorphisms and PCOS risk.

Methods

All eligible trials were identified via systematic searches of multiple literature databases. Outcome data were synthesized by using crude odds ratio with 95% confidence interval. Heterogeneity was assessed with the I² test. Publication bias and subgroup analyses were also performed.

Results

A total of 2449 cases and 1977 controls from nine studies were selected for analysis. The pooled results showed a significant association between PCOS risk and PON1 − 108 C/T polymorphism in the following genetic models [allelic, 0.72 (0.56–0.92); homozygote, 0.51 (0.32–0.82); heterozygote, 0.44 (0.25–0.78); and dominant 0.47 (0.29–0.77)]. For the PON1 192 Q/R polymorphism, a significant relationship was found in the allelic model [0.62 (0.41–0.93)] and recessive model [0.61 (0.37–0.98)]. PCOS risk was also linked to PON1 L55M polymorphism in the heterozygote model [0.62 (0.39–0.98)] and dominant model [0.63 (0.41–0.96)].

Conclusions

Our study has shown that PON1 − 108 C/T polymorphism might be associated with increased risk of PCOS under the allelic, homozygote, heterozygote, and dominant models. Additionally, PON1 192 Q/R and L55M polymorphisms were significantly related only in the allelic and recessive model, and in the heterozygote and dominant model, respectively.

Available only for authorised users

Goodarzi MO, Dumesic DA, Chazenbalk G, Azziz R (2011) Polycystic ovary syndrome: etiology, pathogenesis and diagnosis. Nat Rev Endocrinol 7(4):219–231. https://doi.org/10.1038/nrendo.2010.217 CrossRefPubMed

Pasquali R, Gambineri A (2018) New perspectives on the definition and management of polycystic ovary syndrome. J Endocrinol Invest. https://doi.org/10.1007/s40618-018-0832-1 CrossRefPubMed

Conway G, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Franks S, Gambineri A, Kelestimur F, Macut D, Micic D, Pasquali R, Pfeifer M, Pignatelli D, Pugeat M, Yildiz BO (2014) The polycystic ovary syndrome: a position statement from the European Society of Endocrinology. Eur J Endocrinol 171(4):P1–29. https://doi.org/10.1530/eje-14-0253 CrossRefPubMed

Fauser BC, Tarlatzis BC, Rebar RW, Legro RS, Balen AH, Lobo R, Carmina E, Chang J, Yildiz BO, Laven JS, Boivin J, Petraglia F, Wijeyeratne CN, Norman RJ, Dunaif A, Franks S, Wild RA, Dumesic D, Barnhart K (2012) Consensus on women’s health aspects of polycystic ovary syndrome (PCOS): the Amsterdam ESHRE/ASRM-Sponsored 3rd PCOS Consensus Workshop Group. Fertil Steril 97(1):28–38. https://doi.org/10.1016/j.fertnstert.2011.09.024 CrossRefPubMed

Macut D, Antic IB, Bjekic-Macut J (2015) Cardiovascular risk factors and events in women with androgen excess. J Endocrinol Invest 38(3):295–301. https://doi.org/10.1007/s40618-014-0215-1 CrossRefPubMed

Kucukaydin Z, Duran C, Basaran M, Camlica F, Erdem SS, Basaran A, Kutlu O, Burnik FS, Elmas H, Gonen MS (2016) Plasma total oxidant and antioxidant status after oral glucose tolerance and mixed meal tests in patients with polycystic ovary syndrome. J Endocrinol Invest 39(10):1139–1148. https://doi.org/10.1007/s40618-016-0498-5 CrossRefPubMed

Condorelli RA, Calogero AE, Di Mauro M, Mongioi LM, Cannarella R, Rosta G, La Vignera S (2017) Androgen excess and metabolic disorders in women with PCOS: beyond the body mass index. J Endocrinol Invest. https://doi.org/10.1007/s40618-017-0762-3 CrossRefPubMed

Behboudi-Gandevani S, Ramezani Tehrani F, Bidhendi Yarandi R, Noroozzadeh M, Hedayati M, Azizi F (2017) The association between polycystic ovary syndrome, obesity, and the serum concentration of adipokines. J Endocrinol Invest 40(8):859–866. https://doi.org/10.1007/s40618-017-0650-x CrossRefPubMed

Polak K, Czyzyk A, Simoncini T, Meczekalski B (2017) New markers of insulin resistance in polycystic ovary syndrome. J Endocrinol Invest 40(1):1–8. https://doi.org/10.1007/s40618-016-0523-8 CrossRefPubMed

10.

Diamanti-Kandarakis E, Piperi C (2005) Genetics of polycystic ovary syndrome: searching for the way out of the labyrinth. Hum Reprod Update 11(6):631–643. https://doi.org/10.1093/humupd/dmi025 CrossRefPubMed

11.

Huang M, Xiao J, Zhao X, Liu C, Chen Q (2012) Four polymorphisms of the CAPN 10 gene and their relationship to polycystic ovary syndrome susceptibility: a meta-analysis. Clin Endocrinol 76(3):431–438. https://doi.org/10.1111/j.1365-2265.2011.04218.x CrossRef

12.

Vink JM, Sadrzadeh S, Lambalk CB, Boomsma DI (2006) Heritability of polycystic ovary syndrome in a Dutch twin-family study. J Clin Endocrinol Metab 91(6):2100–2104. https://doi.org/10.1210/jc.2005-1494 CrossRefPubMed

13.

Christopoulos P, Mastorakos G, Gazouli M, Deligeoroglou E, Katsikis I, Diamanti-Kandarakis E, Panidis D, Creatsas G (2010) Study of association of IRS-1 and IRS-2 genes polymorphisms with clinical and metabolic features in women with polycystic ovary syndrome. Is there an impact? Gynecol Endocrinol 26(9):698–703. https://doi.org/10.3109/09513591003649823 CrossRefPubMed

14.

Petry CJ, Ong KK, Michelmore KF, Artigas S, Wingate DL, Balen AH, de Zegher F, Ibanez DB, Dunger L (2005) Association of aromatase (CYP 19) gene variation with features of hyperandrogenism in two populations of young women. Hum Reprod (Oxford, England) 20(7):1837–1843. https://doi.org/10.1093/humrep/deh900 CrossRef

15.

Zhu JQ, Zhu L, Liang XW, Xing FQ, Schatten H, Sun QY (2010) Demethylation of LHR in dehydroepiandrosterone-induced mouse model of polycystic ovary syndrome. Mol Hum Reprod 16(4):260–266. https://doi.org/10.1093/molehr/gap089 CrossRefPubMed

16.

Camps J, Marsillach J, Joven J (2009) The paraoxonases: role in human diseases and methodological difficulties in measurement. Crit Rev Clin Lab Sci 46(2):83–106. https://doi.org/10.1080/10408360802610878 CrossRefPubMed

17.

Sakai T, Matsuura B, Onji M (1998) Serum paraoxonase activity and genotype distribution in Japanese patients with diabetes mellitus. Intern Med (Tokyo, Japan) 37(7):581–584CrossRef

18.

Mackness M, Mackness B (2004) Paraoxonase 1 and atherosclerosis: is the gene or the protein more important? Free Radic Biol Med 37(9):1317–1323. https://doi.org/10.1016/j.freeradbiomed.2004.07.034 CrossRefPubMed

19.

Fenkci IV, Serteser M, Fenkci S, Kose S (2007) Paraoxonase levels in women with polycystic ovary syndrome. J Reprod Med 52(10):879–883PubMed

20.

Mohamadin AM, Habib FA, Elahi TF (2010) Serum paraoxonase 1 activity and oxidant/antioxidant status in Saudi women with polycystic ovary syndrome. Pathophysiology 17(3):189–196. https://doi.org/10.1016/j.pathophys.2009.11.004 CrossRefPubMed

21.

Brophy VH, Jampsa RL, Clendenning JB, McKinstry LA, Jarvik GP, Furlong CE (2001) Effects of 5′ regulatory-region polymorphisms on paraoxonase-gene (PON1) expression. Am J Hum Genet 68(6):1428–1436. https://doi.org/10.1086/320600 CrossRefPubMedPubMedCentral

22.

Dadachanji R, Shaikh N, Khavale S, Patil A, Shah N, Mukherjee S (2015) PON1 polymorphisms are associated with polycystic ovary syndrome susceptibility, related traits, and PON1 activity in Indian women with the syndrome. Fertil Steril 104(1):207–216. https://doi.org/10.1016/j.fertnstert.2015.03.037 CrossRefPubMed

23.

Zhang Y, Liu H, He J, Xu K, Bai H, Wang Y, Zhang F, Zhang J, Cheng L, Fan P (2015) Lactonase activity and status of paraoxonase 1 in Chinese women with polycystic ovarian syndrome. Eur J Endocrinol 172(4):391–402. https://doi.org/10.1530/eje-14-0863 CrossRefPubMed

24.

Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group (2004) Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 19(1):41–47

25.

Zawadzki J, Dunaif A (1992) Diagnostic criteria for polycystic ovary syndrome: towards a rational approach. In: Dunaif A, Givens J, Haseltine F, Haseltine G (eds) Polycystic ovary syndrome, 1st edn. Oxford, England, Blackwell Scientific, pp 377–384

26.

Stang A (2010) Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 25(9):603–605. https://doi.org/10.1007/s10654-010-9491-z CrossRefPubMed

27.

DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7(3):177–188CrossRefPubMed

28.

Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22(4):719–748PubMed

29.

Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ (Clinical research ed) 315(7109):629–634CrossRef

30.

Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50(4):1088–1101CrossRefPubMed

31.

San Millan JL, Corton M, Villuendas G, Sancho J, Peral B, Escobar-Morreale HF (2004) Association of the polycystic ovary syndrome with genomic variants related to insulin resistance, type 2 diabetes mellitus, and obesity. J Clin Endocrinol Metab 89(6):2640–2646. https://doi.org/10.1210/jc.2003-031252 CrossRefPubMed

32.

Mohamed A, Rashed L, Salam R (2009) Effect of paraoxonase gene polymorphisms on paraoxonase levels and insulin resistance index in women with polycystic ovary syndrome. Aust J Basic Appl Sci 3(4):3346–3351

33.

Zhang F, Liu H, Fan P, Bai H, Song Q (2011) The − 108C/T polymorphism in paraoxonase 1 gene in Chinese patients with polycystic ovary syndrome. J Si Chuan Univ (Med Sci Edi) 42(1):24–28

34.

Wang Y, Liu H, Fan P, Bai H, Zhang J, Zhang F (2012) Evidence for association between paraoxonase 1 gene polymorphisms and polycystic ovarian syndrome in southwest Chinese women. Eur J Endocrinol 166(5):877–885. https://doi.org/10.1530/eje-11-0986 CrossRefPubMed

35.

Paltoglou G, Tavernarakis G, Christopoulos P, Vlassi M, Gazouli M, Deligeoroglou E, Creatsas G, Mastorakos G (2013) 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 79(2):259–266. https://doi.org/10.1111/cen.12139 CrossRef

36.

Ferk P, Gersak K (2014) Association of − 108 C>T PON1 polymorphism with polycystic ovary syndrome. Biomed Rep 2(2):255–259. https://doi.org/10.3892/br.2013.214 CrossRefPubMed

37.

Lenarcik A, Bidzinska-Speichert B, Tworowska-Bardzinska U (2010) The role of chronic inflammation and Leu55Met PON1 polymorphism in the pathogenesis of polycystic ovary syndrome. Gynecol Endocrinol 26(9):673–683. https://doi.org/10.3109/09513591003686387 CrossRefPubMed

38.

Durmus U, Duran C, Ecirli S (2017) Visceral adiposity index levels in overweight and/or obese, and non-obese patients with polycystic ovary syndrome and its relationship with metabolic and inflammatory parameters. J Endocrinol Invest 40(5):487–497. https://doi.org/10.1007/s40618-016-0582-x CrossRefPubMed

39.

Franks S, McCarthy MI, Hardy K (2006) Development of polycystic ovary syndrome: involvement of genetic and environmental factors. Int J Androl 29(1):278–285. https://doi.org/10.1111/j.1365-2605.2005.00623.x (discussion 286–290) CrossRefPubMed

40.

Goswami B, Tayal D, Gupta N, Mallika V (2009) Paraoxonase: a multifaceted biomolecule. Clin Chim Acta Int J Clin Chem 410(1–2):1–12. https://doi.org/10.1016/j.cca.2009.09.025 CrossRef

41.

Ben-David M, Elias M, Filippi JJ, Dunach E, Silman I, Sussman JL, Tawfik DS (2012) Catalytic versatility and backups in enzyme active sites: the case of serum paraoxonase 1. J Mol Biol 418(3–4):181–196. https://doi.org/10.1016/j.jmb.2012.02.042 CrossRefPubMed

42.

Precourt LP, Amre D, Denis MC, Lavoie JC, Delvin E, Seidman E, Levy E (2011) The three-gene paraoxonase family: physiologic roles, actions and regulation. Atherosclerosis 214(1):20–36. https://doi.org/10.1016/j.atherosclerosis.2010.08.076 CrossRefPubMed

43.

Ginsberg G, Neafsey P, Hattis D, Guyton KZ, Johns DO, Sonawane B (2009) Genetic polymorphism in paraoxonase 1 (PON1): population distribution of PON1 activity. J Toxicol Environ Health Part B 12(5–6):473–507. https://doi.org/10.1080/10937400903158409 CrossRef

Title: Association of PON1 gene polymorphisms with polycystic ovarian syndrome risk: a meta-analysis of case–control studies
Authors: D. Liao
H. Yu
L. Han
C. Zhong
X. Ran
D. Wang
L. Mo
Publication date: 01-11-2018
Publisher: Springer International Publishing
Published in: Journal of Endocrinological Investigation / Issue 11/2018
Electronic ISSN: 1720-8386
DOI: https://doi.org/10.1007/s40618-018-0866-4

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 11/2018

TSH evaluation in hypothyroid patients assuming liquid levothyroxine at breakfast or 30 min before breakfast

From inflammation to sexual dysfunctions: a journey through diabetes, obesity, and metabolic syndrome

Clinicopathologic risk factors for right paraesophageal lymph node metastasis in patients with papillary thyroid carcinoma

Combined BRAFV600E analysis and 99mTc-MIBI scintigraphy can be a useful diagnostic tool in differentiated thyroid cancer patients with incomplete bio-chemical response to first radioiodine therapy (RAIT): a pilot investigation

Predictors of fat-free mass loss 1 year after laparoscopic sleeve gastrectomy

Lymph node location is a risk factor for papillary thyroid cancer-related death

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials