Vitamin D resistant genes (CYP24A1, SMRT, SNAIL) – July 2022

Vitamin D resistant genes - promising therapeutic targets of chronic diseases

Review Food Funct. 2022 Jul 20. doi: 10.1039/d2fo00822j   $50 paywall
Kunnath Lakshmanan Milan 1, Ravichandran Jayasuriya 1, Kannan Harithpriya 1, Murugesan Anuradha 2, Dronamraju V L Sarada 1, Nadhiroh Siti Rahayu 3, Kunka Mohanram Ramkumar 1

Vitamin D is an essential vitamin indispensable for calcium and phosphate metabolism, and its deficiency has been implicated in several extra-skeletal pathologies, including cancer and chronic kidney disease. Synthesized endogenously in the layers of the skin by the action of UV-B radiation, the vitamin maintains the integrity of the bones, teeth, and muscles and is involved in cell proliferation, differentiation, and immunity. The deficiency of Vit-D is increasing at an alarming rate, with nearly 32% of children and adults being either deficient or having insufficient levels. This has been attributed to Vit-D resistant genes that cause a reduction in circulatory Vit-D levels through a set of signaling pathways.

CYP24A1, SMRT, and SNAIL are three genes responsible for Vit-D resistance as their activity
either lowers the circulatory levels of Vit-D
or reduces its availability in target tissues.

The hydroxylase CYP24A1 inactivates analogs and prohormonal and/or hormonal forms of calcitriol. Elevation of the expression of CYP24A1 is the major cause of exacerbation of several diseases. CYP24A1 is rate-limiting, and its induction has been correlated with increased prognosis of diseases, while loss of function mutations cause hypersensitivity to Vit-D.
The silencing mediator of retinoic acid and thyroid hormone receptor (SMRT) and its corepressor are involved in the transcriptional repression of VDR-target genes.
SNAIL1 (SNAIL), SNAIL2 (Slug), and SNAIL3 (Smuc) are involved in transcriptional repression and binding to histone deacetylases and methyltransferases in addition to recruiting polycomb repressive complexes to the target gene promoters. An inverse relationship between the levels of calcitriol and the epithelial-to-mesenchymal transition is reported. Studies have demonstrated a strong association between Vit-D deficiency and chronic diseases, including cardiovascular diseases, diabetes, cancers, autoimmune diseases, infectious diseases, etc. Vit-D resistant genes associated with the aforementioned chronic diseases could serve as potential therapeutic targets. This review focuses on the basic structures and mechanisms of the repression of Vit-D regulated genes and highlights the role of Vit-D resistant genes in chronic diseases.

$95 PDF can be viewed on DeepDyve - free during trial period

Vitamin D Life - Genetics chart shows the vitamin D genes

Wonder why this study did not include the Vitamin D Receptor - that is deactivated by many diseases and easily re-activated

Vitamin D Life - Cancers might alter CYP24A1 gene

Vitamin D Life pages with CYP24A1 in title (29 as of July 2022)

This list is automatically updated

Vitamin D Life – Sample of Genetics studies

• Vitamin D genes – Review June 2022
• Vitamin D effects on over 300 genes varies with genetics and levels – Dec 2020
• Vitamin D genes are important, update – Sept 2020
• Low Vitamin D in blood is associated with 69 genes, only 6 of which are reported on - Feb 2020
• Does survival of the less fit mean less health (poor genes may be inherited)
• 1289 genes changed with higher doses of Vitamin D - RCT Dec 2019
• Vitamin D affects at least 3,023 DNA locations – July 2018
• 2,776 vitamin D receptor binding sites - April 2014
• 5839 genes changed during pregnancy (many genes were related to Vitamin D) – Oct 2016
• Genes which regulate active vitamin D worsen with age – Oct 2016
• Health problems that run in families are often associated with low vitamin D
• Genes and Vitamin D – literature review – Dec 2015