Molecular insights of vitamin D receptor SNPs and vitamin D analogs: a novel therapeutic avenue for vitiligo

Sakthi Sasikala Sundaravel; Beena Briget Kuriakose; Amani Hamad Alhazmi; Sabareeswari Jeyaraman; Sushma Shruthi Jagannathan; Karthikeyan Muthusamy

doi:10.1007/s11030-025-11168-9

Molecular insights of vitamin D receptor SNPs and vitamin D analogs: a novel therapeutic avenue for vitiligo

Mol Divers. 2025 Mar 21. doi: 10.1007/s11030-025-11168-9. Online ahead of print.

Authors

Sakthi Sasikala Sundaravel¹, Beena Briget Kuriakose², Amani Hamad Alhazmi³, Sabareeswari Jeyaraman¹, Sushma Shruthi Jagannathan¹, Karthikeyan Muthusamy^{4

5}

Affiliations

¹ Pharmacogenomics and CADD Lab, Department of Bioinformatics, Alagappa University, Tamil Nadu, Karaikudi, India.
² Department of Basic Medical Sciences, College of Applied Medical Sciences, King Khalid University, Khamis Mushayt, Saudi Arabia.
³ Department of Public Health, College of Applied Medical Sciences, King Khalid University, Khamis Mushayt, Saudi Arabia.
⁴ Pharmacogenomics and CADD Lab, Department of Bioinformatics, Alagappa University, Tamil Nadu, Karaikudi, India. mkbioinformatics@gmail.com.
⁵ Department of Bioinformatics, Alagappa University, Tamil Nadu, Karaikudi, 630 003, India. mkbioinformatics@gmail.com.

PMID: 40117094
DOI: 10.1007/s11030-025-11168-9

Abstract

Vitamin D receptor (VDR) agonists play a pivotal role in modulating immune responses and promoting melanocyte survival, making them potential candidates for vitiligo treatment. The VDR gene is integral to mediating the effects of vitamin D in the immune system, and disruptions in its structure due to missense mutations may significantly contribute to the pathogenesis of vitiligo. Missense single-nucleotide polymorphisms (SNPs) can alter the amino acid sequence of the VDR protein, potentially affecting its ligand-binding affinity and downstream signaling. Investigating these missense SNPs provides critical insights into the genetic underpinnings of vitiligo and may help identify biomarkers for early detection and precision-targeted therapies. This study explored the therapeutic potential of vitamin D analogs in vitiligo management, with a particular focus on their binding interactions and molecular efficacy. Using molecular docking and virtual screening, 24 vitamin D analogs were evaluated. Calcipotriol exhibited the highest binding affinity (-11.4 kcal/mol) and unique interactions with key residues in the VDR ligand-binding domain. Additionally, an analysis of structural variations stemming from missense mutations in the VDR gene highlighted potential impacts on receptor-ligand interactions, further emphasizing the importance of genetic factors in treatment response. These findings underscore the potential of calcipotriol to promote melanogenesis and modulate pigmentation in vitiligo. A comparative analysis identified structural variations influencing the efficacy of other analogs, such as calcitriol and tacalcitol. Although the in silico methods provided valuable insights, the study acknowledges the limitations of excluding dynamic cellular environments and emphasizes the need for experimental validation. Overall, this study enhances our understanding of VDR-targeted therapies, and calcipotriol is a promising candidate for further development in the management of vitiligo.

Keywords: Calcipotriol; Melanogenesis; Molecular docking; Vitamin D receptor (VDR) analogs; Vitiligo management.