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DOI: 10.1055/a-1587-9336
Polymorphisms of Vitamin D Receptor and the Effect on Metabolic and Endocrine Abnormalities in Polycystic Ovary Syndrome: A Review
Abstract
Polycystic ovary syndrome (PCOS) is one of the most prevalent endocrine disorder in women of reproductive age. Vitamin D and its receptor are thought to play an important role in PCOS susceptibility, although the impact of vitamin D receptor (VDR) polymorphisms on the hormonal and metabolic profile is still controversial. A literature search in PubMed and Embase was performed up to September 2020 for case-control studies in women suffering from PCOS, with outcome related to VDR polymorphisms effect on metabolic/endocrine disturbances. We have found 16 eligible studies including 2566 women with PCOS and 2430 controls. ApaI polymorphism seemed to be associated with hyperandrogenism in both Asian and Caucasian population. FokI variant was correlated with metabolic/endocrine parameters especially in Asian population, while a relation between Cdx2 genotypes and insulin sensitivity was observed in both ethnicities. VDR polymorphisms have an important role in PCOS development and related hormonal and metabolic abnormalities. Few case-control studies analysed the interaction between VDR variants and metabolic/endocrine parameters with the majority of the articles focused on the Asian region. Further research on various ethnic populations with larger sample size are still needed for a definitive conclusion, in order to allow early diagnosis and prevention of PCOS comorbidities.
Publikationsverlauf
Eingereicht: 22. Februar 2021
Angenommen nach Revision: 07. Juni 2021
Artikel online veröffentlicht:
20. September 2021
© 2021. Thieme. All rights reserved.
Georg Thieme Verlag KG
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References
- 1 Azziz R, Carmina E, Chen Z. et al. Polycystic ovary syndrome. Nat Rev Dis Primers 2016; 2: 1-18
- 2 Lizneva D, Suturina L, Walker W. et al. Criteria, prevalence, and phenotypes of polycystic ovary syndrome. Fertil Steril 2016; 106: 6-15
- 3 Reis GVOP, Gontijo NA, Rodrigues KF. et al. Vitamin D receptor polymorphisms and the polycystic ovary syndrome: A systematic review. J Obstet Gynaecol Res 2017; 43: 436-446
- 4 Bozdag G, Mumusoglu S, Zengin D. et al. The prevalence and phenotypic features of polycystic ovary syndrome: A systematic review and meta-analysis. Hum Reprod 2016; 31: 2841-2855
- 5 Andrade VH, Mata AM, Borges RS. et al. Current aspects of polycystic ovary syndrome: a literature review. Rev Assoc Med Bras 2016; 62: 867-871
- 6 Bednarska S, Siejka A. The pathogenesis and treatment of polycystic ovary syndrome: what's new?. Adv Clin Exp Med 2017; 26: 359-367
- 7 De Leo V, Musacchio MC, Cappelli V. et al. Genetic, hormonal and metabolic aspects of PCOS: an update. Reprod Biol Endocrinol 2016; 14: 38
- 8 Carvalho LML, Dos Reis FM, Candido AL. et al. Polycystic ovary syndrome as a systemic disease with multiple molecular pathways: A narrative review. Endocr Regul 2018; 52: 208-221
- 9 Ozdemir S, Ozdemir M, Görkemli H. et al. Specific dermatologic features of the polycystic ovary syndrome and its association with biochemical markers of the metabolic syndrome and hyperandrogenism. Acta Obstet Gynecol Scand 2010; 89: 199-204
- 10 Hong JS, Kwon HH, Park SY. et al. Cutaneous manifestations of the subtypes of polycystic ovary syndrome in Korean patients. J Eur Acad Dermatol Venereol 2015; 29: 42-47
- 11 Feng JG, Guo Y, Ma LA. et al. Prevalence of dermatologic manifestations and metabolic biomarkers in women with polycystic ovary syndrome in north China. J Cosmet Dermatol 2018; 17: 511-517
- 12 Neven ACH, Laven J, Teede HJ. et al. Summary on polycystic ovary syndrome: diagnostic criteria, prevalence, clinical manifestations, and management according to the latest international guidelines. Semin Reprod Med 2018; 36: 5-12
- 13 Nyagolova PV, Mitkov MD, Orbetsova MM. Role of vitamin D and adipose tissue hormones in women with reproductive disorders. Folia Med (Plovdiv) 2015; 57: 5-10
- 14 Niu YM, Wang YD, Jiang GB. et al. Association between vitamin D receptor gene polymorphisms and polycystic ovary syndrome risk: A meta-analysis. Front Physiol 2019; 9: 1902
- 15 Liang F, Ren N, Zhang H. et al. A meta-analysis of the relationship between vitamin D receptor gene ApaI polymorphisms and polycystic ovary syndrome. Adv Clin Exp Med 2019; 28: 255-262
- 16 Wehr E, Trummer O, Giuliani A. et al. Vitamin D-associated polymorphisms are related to insulin resistance and vitamin D deficiency in polycystic ovary syndrome. Eur J Endocrinol 2011; 164: 741-749
- 17 Siddamalla S, Reddy TV, Govatati S. et al. Vitamin D receptor gene polymorphisms and risk of polycystic ovary syndrome in South Indian women. Gynecol Endocrinol 2018; 34: 161-165
- 18 Song DK, Lee H, Hong YS. et al. Vitamin D receptor and binding protein polymorphisms in women with polycystic ovary syndrome: A case control study. BMC Endocr Disord 2019; 19: 145
- 19 Shi XY, Huang AP, Xie DW. et al. Association of vitamin D receptor gene variants with polycystic ovary syndrome: A meta-analysis. BMC Med Genet 2019; 20: 32
- 20 El-Shal AS, Shalaby SM, Aly NM. et al. 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: 6063-6073
- 21 Al Thomali A, Daghestani MH, Daghestani MH. et al. Polymorphic variations in VDR gene in Saudi women with and without polycystic ovary syndrome (PCOS) and significant influence of seven polymorphic sites on anthropometric and hormonal parameters. J Med Biochem 2018; 37: 415-425
- 22 Zadeh-Vakili A, Ramezani TF, Daneshpour MS. et al. Genetic polymorphism of vitamin D receptor gene affects the phenotype of PCOS. Gene 2013; 515: 193-196
- 23 Xavier LB, Gontijo NA, Rodrigues KF. et al. Polymorphisms in vitamin D receptor gene, but not vitamin D levels, are associated with polycystic ovary syndrome in Brazilian women. Gynecol Endocrinol 2019; 35: 146-149
- 24 Vasilovici AF, Grigore LE, Ungureanu L. et al. Vitamin D receptor polymorphisms and melanoma. Oncol Lett 2019; 17: 4162-4169
- 25 Uitterlinden AG, Fang Y, Van Meurs JB. et al. Genetics and biology of vitamin D receptor polymorphisms. Gene 2004; 338: 143-156
- 26 Mahmoudi T. Genetic variation in the vitamin D receptor and polycystic ovary syndrome risk. Fertil Steril 2009; 92: 1381-1383
- 27 Dasgupta S, Dutta J, Annamaneni S. et al. Association of vitamin D receptor gene polymorphisms with polycystic ovary syndrome among Indian women. Indian J Med Res 2015; 142: 276-285
- 28 Humadi EH, Showman HA, Al-azzawie RMHF. Association of vitamin-D receptor gene polymorphisms (FokI and ApaI) and vitamin D serum levels in a sample of Iraqi women with polycystic ovary syndrome. Indian J Public Health Res Dev 2018; 9: 867-874
- 29 Jedrzejuk 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: 976-979
- 30 Szafarowska M, Dziech E, Kaleta B. et al. Anti-Müllerian hormone level is associated with vitamin D receptor polymorphisms in women with polycystic ovary syndrome. J Assist Reprod Genet 2019; 36: 1281-1289
- 31 Dipanshu S, Chakravorty R. Genetic polymorphism in the vitamin D receptor gene and 25-hydroxyvitamin D serum levels in East Indian women with polycystic ovary syndrome. J Mol Biomark Diagn 2015; 6: 247
- 32 Santos BR, Lecke SB, Spritzer PM. Apa-I polymorphism in VDR gene is related to metabolic syndrome in polycystic ovary syndrome: A cross-sectional study. Reprod Biol Endocrinol 2018; 16: 38
- 33 Kadhim SJ, Abdul-hassan IA. Correlation between vitamin D receptor gene polymorphisms and levels of some hormones in Iraqi infertile women with polycystic ovary syndrome. Iraqi J Biotechnol 2017; 16: 104-113
- 34 Mahmoudi T, Majidzadeh-AK, Farahani H et al. Association of vitamin D receptor gene variants with polycystic ovary syndrome: A case control study. Int J Reprod Biomed 2015; 13: 793–800
- 35 Bagheri M, Rad IA, Jazani NH. et al. Lack of association of vitamin D receptor FokI (rs10735810) (C/T) and BsmI (rs1544410) (A/G) genetic variations with polycystic ovary syndrome risk: a case-control study from Iranian Azeri Turkish women. Maedica (Bucur) 2012; 7: 303-308
- 36 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: 225-232
- 37 Ramezani N, Ostadsharif M, Nayeri H. Association of BsmI variant of vitamin D receptor gene with polycystic ovary syndrome: A case-control study. Int J Reprod BioMed 2020; 18: 877-884
- 38 Bagheri M, Abdi RI, Hosseini JN. et al. Vitamin D receptor TaqI gene variant in exon 9 and polycystic ovary syndrome risk. Int J Fertil Steril 2013; 7: 116-121
- 39 Hamdi RA, Abdul-Qahar ZH, Ahmed SJ. et al. Assessment of vitamin D receptor gene polymorphism in Iraqi women with polycystic ovary syndrome. J Clin Diagnostic Res 2018; 12: 27-30
- 40 Wang Y, Zhu J, DeLuca HF. Where is the vitamin D receptor?. Arch Biochem Biophys 2012; 523: 123-133
- 41 Szymczak-Pajor I, Śliwińska A. Analysis of association between vitamin D deficiency and insulin resistance. Nutrients 2019; 11: 794
- 42 Hahn S, Haselhorst U, Tan S. et al. Low serum 25-hydroxyvitamin D concentrations are associated with insulin resistance and obesity in women with polycystic ovary syndrome. Exp Clin Endocrinol Diabetes 2006; 114: 577-583
- 43 Al-Bayyari N, Al-Domi H, Zayed F. et al. Androgens and hirsutism score of overweight women with polycystic ovary syndrome improved after vitamin D treatment: A randomized placebo controlled clinical trial. Clin Nutr 2021; 40: 870-878