THE INVOLVEMENT OF VDR PROMOTER METHYLATION, CDX-2 VDR POLYMORPHISM AND VITAMIN D LEVELS IN MALE INFERTILITY

• Published in: Acta endocrinologica (Bucharest, Romania : 2005) Vol. 13; no. 3; pp. 294 - 301
• Main Authors: Vladoiu, S, Botezatu, A, Anton, G, Manda, D, Paun, D L, Oros, S, Rosca, R, Dinu Draganescu, D
• Format: Journal Article
• Language: English
• Published: Romania Acta Endocrinologica Foundation 01-07-2017
• Subjects: General Endocrinology; VDR Cdx-2 polymorphism; male infertility; vitamin D; epigenetics
• ISSN: 1841-0987; 1843-066X
• DOI: 10.4183/aeb.2017.294

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.
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.
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.
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.
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.