July - September 2017, Volume 13, Issue 3

Vladoiu S, Botezatu A, Anton G, Manda D, Paun DL, Oros S, Rosca R, Dinu Draganescu D

The Involvement of VDR Promoter Methylation, CDX-2 VDR Polymorphism and Vitamin D Levels in Male Infertility

Acta Endo (Buc) 2017, 13 (3): 294-301
doi: 10.4183/aeb.2017.294

Introduction. Vitamin D (VD) levels were correlated with different health conditions, including reproductive disorders in males. Vitamin D action is mediated through vitamin D receptor (VDR), which acts as a transcription factor. VDR gene promoter is embedded in a GC-rich island. The VDR gene has been shown to have several polymorphisms that affect the receptor function. Aim. To examine the relationship between Cdx- 2 polymorphism (rs17883968), the methylation status of VDR’s promoter and serum levels of 25-hydroxyvitamin D in male infertility. Patients and Methods. A total of 69 infertile men and 37 age-matched controls were enrolled in this study. Vitamin D level assessments were detected using the electrochemiluminescent method. Cdx-2 VDR polymorphism identification was performed by PCR on DNA samples from blood, followed by restriction. Methylation of VDR gene promoter was assessed by qMS-PCR using bisulfite-treated DNA from fresh sperm. Results. Vitamin D levels was found to be significantly decreased in infertile groups compared the controls (p=0.0279). The GG genotype was found in a higher percentage in controls and the AA genotype was higher in infertile group (p=0.0056). Infertile homozygote (GG) and heterozygote (GA) individuals had significantly higher vitamin D levels than AA homozygote. Methylation is higher in individuals with lower vitamin D levels and AA genotype is characterized by higher methylation values. Conclusion. The results provide new insights of Cdx-2 polymorphism is involved in vitamin D deficiency, highlighting the important role of epigenetic modification of vitamin D receptor and male infertility along with the genetic context.

Keywords: epigenetics, male infertility, vitamin D, VDR Cdx-2 polymorphism

Correspondence: Gabriela Anton, “Stefan S. Nicolau” Virology Institute, Research, 285 Mihai Bravu Ave., Bucharest, 030304, Romania, E-mail: gnanka30@yahoo.com