Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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Advances in Clinical and Experimental Medicine

2019, vol. 28, nr 2, February, p. 255–262

doi: 10.17219/acem/85882

Publication type: original article

Language: English

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A meta-analysis of the relationship between vitamin D receptor gene ApaI polymorphisms and polycystic ovary syndrome

Fang Liang1,A,B,D,E, Na Ren2,A,D,E, Hongxia Zhang1,C, Jian Zhang1,E, Qingguo Wu1,D, Rui Song1,B, Zhenfeng Shi1,E, Zhanxiu Zhang3,B, Kuixiang Wang3,B,E,F

1 Departments of Endocrinology, Xingtai People’s Hospital, Hebei Medical University, China

2 Departments of Endocrinology, 3rd Xiangya Hospital of Central South University, Changsha, China

3 Departments of Joint Orthopedics, Xingtai People’s Hospital, Hebei Medical University, China

Abstract

Background. Emerging evidence from pre-clinical and clinical studies has shown that vitamin D (VD) plays an important role in the pathogenesis of polycystic ovary syndrome (PCOS). Potentially functional ApaI polymorphism of vitamin D receptor (VDR) gene has been implicated in PCOS risk, but individually published studies have yielded inconclusive results.
Objectives. Studies on the associations of VDR gene polymorphisms with PCOS susceptibility reported conflicting results. The objective of this study was to perform a systematic meta-analysis to clarify this issue.
Material and Methods. We searched for all publications regarding the associations mentioned above in PubMed, Web of Science, Embase, and China National Knowledge Infrastructure (CNKI) databases updated up to April 2017. A meta-analysis of the overall odds ratios (ORs) with 95% confidence interval (CI) was calculated with the fixed or random effect model.
Results. A total of 7 studies fulfilling the inclusion criteria were included in this meta-analysis (1,350 cases and 960 controls). Pooled ORs showed a significant association between ApaI polymorphism and PCOS risk in all 4 genetic models. Subgroup analysis by ethnicity showed that ApaI polymorphism was associated with the risk of PCOS in Asians (aa vs AA: OR = 1.54, 95% CI = 1.04–2.28, p = 0.03). However, ApaI polymorphism (a vs A: OR = 1.34, 95% CI = 1.00–1.79, p = 0.02; aa+Aa vs AA: OR = 1.36, 95% CI = 1.04–1.79, p = 0.03) was associated with the risk of PCOS in Caucasians.
Conclusion. Our meta-analysis demonstrated that PCOS risk was significantly associated with VDR gene ApaI polymorphism. However, due to the relatively small sample size in this meta-analysis, further studies with a larger sample size should be conducted to confirm the findings.

Key words

meta-analysis, polycystic ovary syndrome, vitamin D receptor, genetic polymorphisms, ApaI

References (33)

  1. Ranjzad F, Mahban A, Shemirani AI, et al. Influence of gene variants related to calcium homeostasis on biochemical parameters of women with polycystic ovary syndrome. J Assist Reprod Genet. 2011;28(3):225–232.
  2. Dunaif A. Insulin resistance and the polycystic ovary syndrome: Mechanism and implications for pathogenesis. Endocr Rev. 1997;18(6):774–800.
  3. Diamanti KE, Kouli CR, Bergiele AT, et al. A survey of the polycystic ovary syndrome in the Greek island of Lesbos: Hormonal and metabolic profile. J Clin Endocrinol Metab. 1999;84(11):4006–4011.
  4. Asunción M, Calvo RM, San Millán JL, Sancho J, Avila S, Escobar-Morreale HF. A prospective study of the prevalence of the polycystic ovary syndrome in unselected Caucasian women from Spain. J Clin Endocrinol Metab. 2000;85(7):2434–2438.
  5. Voulgaris N, Papanastasiou L, Piaditis G, et al. Vitamin D and aspects of female fertility. Hormones (Athens). 2017;16(1):5–21.
  6. Okoroh EM, Boulet SL, George MG, Craig Hooper W. Assessing the intersection of cardiovascular disease, venous thromboembolism, and polycystic ovary syndrome. Thromb Res. 2015;136(6):1165–1168.
  7. Deligeoroglou E, Karountzos V. Dysfunctional uterine bleeding as an early sign of polycystic ovary syndrome during adolescence: An update. Minerva Ginecol. 2017;69(1):68–74.
  8. Gunning MN, Fauser BCJM. Are women with polycystic ovary syndrome at increased cardiovascular disease risk later in life? Climacteric. 2017;20(3):222–227.
  9. Shafiee MN, Seedhouse C, Mongan N, et al. Up-regulation of genes involved in the insulin signaling pathway (IGF1, PTEN and IGFBP1) in the endometrium may link polycystic ovarian syndrome and endometrial cancer. Mol Cell Endocrinol. 2016;424:94–101.
  10. Condorelli RA, Calogero AE, Di Mauro M, La Vignera S. PCOS and diabetes mellitus: From insulin resistance to altered beta pancreatic function, a link in evolution. Gynecol Endocrinol. 2017;33(9):665–667.
  11. Al Nofal A, Viers LD, Javed A. Can the source of hyperandrogenism in adolescents with polycystic ovary syndrome predict metabolic phenotype? Gynecol Endocrinol. 2017;33(11):882–887.
  12. Lazúrová I, Figurová J, Lazúrová Z. Diagnostics of polycystic ovary syndrome [in Czech]. Vnitr Lek. 2015;61(Suppl 5):40–44.
  13. Gruber BM. The phenomenon of vitamin D [in Polish]. Postepy Hig Med Dosw (Online). 2015;69:127–139.
  14. Trochoutsou AI, Kloukina V, Samitas K, Xanthou G. Vitamin-D in the immune system: Genomic and non-genomic actions. Mini Rev Med Chem. 2015;15(11):953–963.
  15. Macut D, Bjekić-Macut J, Rahelić D, Doknić M. Insulin and the polycystic ovary syndrome. Diabetes Res Clin Pract. 2017;130:163–170.
  16. He C, Lin Z, Robb SW, Ezeamama AE. Serum vitamin D levels and polycystic ovary syndrome: A systematic review and meta-analysis. Nutrients. 2015;7(6):4555–4577.
  17. Liu Z, Liu L, Chen X, He W, Yu X. Associations study of vitamin D receptor gene polymorphisms with diabetic microvascular complications: A meta-analysis. Gene. 2014;546(1):6–10.
  18. Zadeh-Vakili A, Ramezani Tehrani F, Daneshpour MS, Zarkesh M, Saadat N, Azizi F. Genetic polymorphism of vitamin D receptor gene affects the phenotype of PCOS. Gene. 2013;515(1):193–196.
  19. Wehr E, Trummer O, Giuliani A, Gruber HJ, Pieber TR, Obermayer-Pietsch B. Vitamin D-associated polymorphisms are related to insulin resistance and vitamin D deficiency in polycystic ovary syndrome. Eur J Endocrinol. 2011;164(5):741–749.
  20. Jędrzejuk D, Łaczmański Ł, Milewicz A, et al. Classic PCOS phenotype is not associated with deficiency of endogenous vitamin D and VDR gene polymorphisms rs731236 (TaqI), rs7975232 (ApaI), rs1544410 (BsmI), rs10735810 (FokI): A case-control study of lower Silesian women. Gynecol Endocrinol. 2015;31(12):976–979.
  21. Mahmoudi T, Majidzadeh-A K, Farahani H, et al. Association of vitamin D receptor gene variants with polycystic ovary syndrome: A case control study. Int J Reprod Biomed (Yazd). 2015;13(12):793–800.
  22. Dasgupta S, Dutta J, Annamaneni S, Kudugunti N, Battini MR. Association of vitamin D receptor gene polymorphisms with polycystic ovary syndrome among Indian women. Indian J Med Res. 2015;142(3):276–285.
  23. El-Shal AS, Shalaby SM, Aly NM, Abdelaziz AM. Genetic variation in the vitamin D receptor gene and vitamin D serum levels in Egyptian women with polycystic ovary syndrome. Mol Biol Rep. 2013;40(11):6063–6073.
  24. Mahmoudi T. Genetic variation in the vitamin D receptor and polycystic ovary syndrome risk. Fertil Steril. 2009;92(4):1381–1383.
  25. Wehr E, Trummer O, Giuliani A, Gruber HJ, Pieber TR, Obermayer-Pietsch B. Vitamin D-associated polymorphisms are related to insulin resistance and vitamin D deficiency in polycystic ovary syndrome. Eur J Endocrinol. 2011;164(5):741–749.
  26. Huabin CAO, Ling TU. Association between vitamin D receptor gene polymorphism and polycystic ovary syndrome. Pract Clin Med. 2017;17:40–53.
  27. Santos BR, Mascarenhas LP, Satler F, Boguszewski MCS, Spritzer PM. Vitamin D receptor gene polymorphisms and sex steroid secretion in girls with precocious pubarche in southern Brazil: A pilot study. J Endocrinol Invest. 2012;35(8):725–729.
  28. Fenichel P, Rougier C, Hieronimus S, Chevalier N. Which origin for polycystic ovaries syndrome: Genetic, environmental or both? Ann Endocrinol (Paris). 2017;78(3):176–185.
  29. Sahin OA, Goksen D, Ozpinar A, Serdar M, Onay H. Association of vitamin D receptor polymorphisms and type 1 diabetes susceptibility in children: A meta-analysis. Endocr Connect. 2017;6(3):159–171.
  30. Wang Q, Xi B, Reilly KH, Liu M, Fu M. Quantitative assessment of the associations between four polymorphisms (FokI, ApaI, BsmI, TaqI) of vitamin D receptor gene and risk of diabetes mellitus. Mol Biol Rep. 2012;39(10):9405–9414.
  31. Areeshi MY, Mandal RK, Dar SA, et al. A reappraised meta-analysis of the genetic association between vitamin D receptor BsmI(rs1544410) polymorphism and pulmonary tuberculosis risk. Biosci Rep. 2017;37(3):BSR20170247.
  32. Yu M, Chen GQ, Yu F. Lack of association between vitamin D receptor polymorphisms ApaI (rs7975232) and BsmI (rs1544410) and osteoporosis among the Han Chinese population: A meta-analysis. Kaohsiung J Med Sci. 2016;32(12):599–606.
  33. Liang F, Wang K, Zhang H, et al. Serum 25-hydroxyvitamin D levels and diabetic retinopathy: A systematic meta-analysis. Int J Clin Exp Pathol. 2016;9(12):12843–12848.
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