Association of vitamin D receptor (VDR) gene polymorphism with embryological characteristics and effectiveness of in vitro fertilization programs
Objective. To study the significance of vitamin D receptor (VDR) gene polymorphism as a molecular genetic marker for estimating the rate of implantation and clinical pregnancy and the patterns of oogenesis and embryogenesis in assisted reproductive technology programs. Subjects and methods. A total of 142 patients who had undergone an in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) program with superovulation and embryo transfer in this cycle were examined during a prospective study case-control study. Serum 25-hydroxyvitamin D levels and VDR gene polymorphism were ascertained in all the patients. The women were divided into 3 groups according to the level of vitamin D; 1) blood vitamin D deficiency (<10 ng/ml); 2) blood vitamin D insufficiency (10-29 ng/ml); 3) normal blood vitamin D levels (30–100 ng/ml). Results. Analysis of the association of VDR gene polymorphism with serum vitamin D levels established that the patients with A/G and A/A genotypes of VDR gene polymorphism: 2A>G (Lys2Arg) (FokI) [rs 10735810] had serum vitamin D deficiency in 13.4% of women, vitamin D insufficiency in 70.1%, and normal vitamin D levels in 16.5% of the women included in the study. At the same time, the patients with G/G genotype of VDR gene polymorphism: 2A>G (Lys2Arg) (FokI) were found to have blood vitamin D deficiency in 40% and insufficiency of this vitamin in 60%. The findings suggest that the carriage of G/G genotype of this polymorphism more than doubles the risk of serum vitamin D deficiency. The analysis of the association of VDR gene polymorphism: 2A>G (Lys2Arg) (FokI) with the quality of the embryos obtained from women with different serum vitamin D levels revealed that the carriage of G/G genotype of the polymorphism (compared to A/A and A/G genotypes) reduced the risk of having poor-quality embryos by more than 3 times. Conclusion. VDR gene polymorphism: 2A>G (Lys2Arg) (FokI) [rs 10735810] is an independent factor that can predict the serum vitamin D level that affects the outcomes of assisted reproductive technology programs and embryo quality and can complement the arsenal of already existing markers.Naimi Z.M.S., Kalinina E.A., Donnikov A.E., Dudarova A.Kh.
Keywords
gene polymorphisms
molecular genetic markers
vitamin D
infertility
stimulated cycle
in vitro fertilization
vitamin D receptor
Supplementary Materials
- Table 1. Ноrmonal profile of patients under research
- Table 2. Embryological characteristics of patients under research
- Pic. 1. Assosiation between polymorphism of the VDR 2A>G (Lys2Arg) (FokI) gene and the level of vitamin D in blood serum (* - allele А or G)
- Pic. 2. Number of bad quality embryos (in %) depending on polymorphism of the VDR 2A>G (Lys2Arg) (FokI) gene and the level of vitamin D in blood serum (* - allele А or G)
References
1. Schwartz G.Ya. Vitamin D and D-hormone. Moscow: Anacharsis; 2005. 152p. (in Russian)
2. Castro L.C. The vitamin D endocrine system. Arq. Bras. Endocrinol. Metabol. 2011; 55(8): 566-75.
3. Lerchbaum E., Obermayer-Pietsch B. Vitamin D and fertility: a systematic review. Eur. J. Endocrinol. 2012; 166(5): 765-78.
4. Wagner C.L., Taylor S.N., Dawodu A., Johnson D.D., Hollis B.W. Vitamin D and its role during pregnancy in attaining optimal health of mother and fetus. Nutrients. 2012; 4(3): 208-30.
5. Christakos S., Ajibade D.V., Dhawan P., Fechner A.J., Mady L.J. Vitamin D: metabolism. Endocrinol. Metab. Clin. North Am. 2010; 39(2): 243-53.
6. Christakos S., Raval-Pandya M., Wernyj R.P., Yang W. Genomic mechanisms involved in the pleiotropic actions of 1,25-dihydroxyvitamin D3. Biochem. J. 2006; 316(Pt 2): 361-71.
7. Merewood A., Mehta S.D., Chen T.C., Bauchner H., Holick M.F. Association between vitamin D deficiency and primary cesarean section. J. Clin. Endocrinol. Metab. 2009; 94(3): 940-5.
8. Dambaher M.A., Schacht E. Osteoporosis and active metabolites of vitamin D: the thoughts that come to mind. Basel: Eular Publ.; 2006. 139p. (in Russian)
9. Erben R.G., Soegiarto D.W., Weber K., Zeitz U., Lieberherr M., Gniadecki R. et al. Deletion of deoxyribonucleic acid binding domain of the vitamin D receptor abrogates genomic and nongenomic functions of vitamin D. Mol. Endocrinol. 2002; 16(7): 1524-37.
10. Christakos S., Dhawan P., Benn B., Porta A., Hediger M., Oh G.T. et al. Vitamin D: molecular mechanism of action. Ann. N. Y. Acad. Sci. 2007; 1116: 340-8.
11. Christakos S., Barletta F., Huening M., Dhawan P., Liu Y., Porta A., Peng X. Vitamin D target proteins: function and regulation. J. Cell. Biochem. 2003; 88(2): 238-44.
12. Kinuta K., Tanaka H., Moriwake T., Aya K., Kato S., Seino Y. Vitamin D is an important factor in estrogen biosynthesis of both female and male gonads. Endocrinology. 2000; 141(4): 1317-24.
13. Ji G.R., Yao M., Sun C.Y., Li Z.H., Han Z. BsmI, TaqI, ApaI and FokI polymorphisms in the vitamin D receptor (VDR) gene and risk of fracture in Caucasians: a meta-analysis. Bone. 2010; 47(3): 681-6.
14. Palomba S., Orio F. Jr., Russo T., Falbo A., Tolino A., Manguso F. et al. BsmI vitamin D receptor genotypes influence the efficacy of antiresorptive treatments in postmenopausal osteoporotic women. A 1-year multicenter, randomized and controlled trial. Osteoporos. Int. 2005; 16(8): 943-52.
15. Cavalcante I.G., Silva A.S., Costa M.J., Persuhn D.C., Issa C.I., Freire T.L., Goncalves M.D. Effect of vitamin D3 supplementation and influence of BsmI polymorphism of the VDR gene of the inflammatory profile and oxidative stress in elderly women with vitamin D insufficiency: Vitamin D3 megadose reduces inflammatory markers. Exp. Gerontol. 2015; 66: 10-6.
16. Laaksonen M.M., Outila T.A., Karkkainen M.U., Kemi V.E., Rita H.J., Perola M. et al. Associations of vitamin D receptor, calcium-sensing receptor and parathyroid hormone gene polymorphisms with calcium homeostasis and peripheral bone density in adult Finns. J. Nutrigenet. Nutrigenomics. 2009;2(2): 55-63.
17. Gentil P., de Lima Lins T.C., Lima R.M., de Abreu B.S., Grattapaglia D., Bottaro M. et al. Vitamin-D-receptor genotypes and bone-mineral density in postmenopausal women: interaction with physical activity. J. Aging Phys. Act. 2009; 17(1): 31-45.
18. Alpha Scientists in Reproductive Medicine and ESHRE Special Interest Group of Embryology.The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Hum. Reprod. 2011; 26(6): 1270-83.
19. Ozkan S., Jindal S., Greenseid K., Shu J., Zeitlian G., Hickmon C., Pal L. Replete vitamin D stores predict reproductive success following in vitro fertilization. Fertil. Steril. 2010; 94(4): 1314-9.
20. Polyzos N.P., Anckaert E., Guzman L., Schiettecatte J., Van Landuyt L., Camus M. et al. Vitamin D deficiency and pregnancy rates in women undergoing single embryo, blastocyst stage, transfer (SET) for IVF/ICSI. Hum. Reprod. 2014; 29(9): 2032-40.
21. Budick B.J., Ingles S.A., Chung K., Stanczyk F.Z., Paulson R.J., Bendikson K.A. Influence of vitamin D levels on in vitro fertilization outcomes in donor- recipient cycles. Fertil. Steril. 2014; 101(2): 447-52.
22. Vladimirova I.V., Kalinina E.A., Donnikov A.E. Molecular genetic markers as prognostic factors of an ovarian response in assisted reproductive technology programs (a review of literature). Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2014; (3): 16-20. (in Russian)
Received 03.11.2016
Accepted 11.11.2016
About the Authors
Naimi Zokhra Mokhamad Sami, graduate student of department of assisted reproductive technology in treating sterility, Research Center of Obstetrics,Gynecology and Perinatology, Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +74954382501. E-mail: naimi-zohra@mail.ru
Kalinina Elena Anatolievna, MD, The chief of department of assisted reproductive technology in treating sterility, Research Center of Obstetrics,
Gynecology and Perinatology, Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +74954381341. E-mail: e_kalinina@oparina4.ru
Donnikov Andrew Evgenievich, PhD, Senior Researcher of molecul-genetical laboratory, Research Center of Obstetrics, Gynecology and Perinatology,
Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +74954381341. E-mail: a_donnikov@oparina4.ru
Dudarova Alina Khasanovna, graduate student of department of assisted reproductive technology in treating sterility, Research Center of Obstetrics,
Gynecology and Perinatology, Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +74954382501. E-mail: kanshaov85@mail.ru
For citations: Naimi Z.M.S., Kalinina E.A., Donnikov A.E., Dudarova A.Kh. Association of vitamin D receptor (VDR) gene polymorphism with embryological characteristics and effectiveness of in vitro fertilization programs. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2017; (2): 51-7. (in Russian)
http://dx.doi.org/10.18565/aig.2017.2.51-7
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