A poor gene (SDR42E1) can greatly reduce Vitamin D from the sun (may be prevalent in the Middle East) – Aug 2024

All 3 publications have the same Middle East author

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Functional characterization of the SDR42E1 reveals its role in vitamin D biosynthesis – Aug 2024

Heliyon (Cell Press) https://doi.org/10.1016/j.heliyon.2024.e36466
Nagham Nafiz Hendi, Maria Teresa Bengoechea-Alonso, Johan Ericsson, Georges Nemer

Highlights

• SDR42E1 knockout alters key vitamin D synthesis regulators: EBP, DHCR7, ALPP, and CYP26A1.
• Multi-omics reveal SDR42E1’s broad role in steroid synthesis and lipid metabolism.
• SDR42E1 knockout accumulates 7-dehydrocholesterol, hindering vitamin D production.
• SDR42E1 variant presents a promising target for addressing vitamin D deficiency.

Vitamin D deficiency poses a widespread health challenge, shaped by environmental and genetic determinants. A recent discovery identified a genetic regulator, rs11542462, in the SDR42E1 gene, though its biological implications remain largely unexplored. Our bioinformatic assessments revealed pronounced SDR42E1 expression in skin keratinocytes and the analogous HaCat human keratinocyte cell lines, prompting us to select the latter as an experimental model. Employing CRISPR/Cas9 gene-editing technology and multi-omics approach, we discovered that depleting SDR42E1 showed a 1.6-fold disruption in steroid biosynthesis pathway (P-value = 0.03), considerably affecting crucial vitamin D biosynthesis regulators. Notably, SERPINB2 (P-value = 2.17 x 10−103), EBP (P-value = 2.46 x 10−13), and DHCR7 (P-value = 8.03 x 10−09) elevated by ∼2-3 fold, while ALPP (P-value < 2.2 x 10−308), SLC7A5 (P-value = 1.96 x 10−215), and CYP26A1 (P-value = 1.06 x 10−08) downregulated by ∼1.5-3 fold. These alterations resulted in accumulation of 7-dehydrocholesterol and reduction of vitamin D production, as evidenced by the drug enrichment (P-value = 4.39 x 10−06) and vitamin D quantification (R2 = 0.935, P-value = 0.0016) analyses. Our investigation unveils SDR42E1's significance in vitamin D homeostasis, emphasizing the potential of precision medicine in addressing vitamin D deficiency through understanding its genetic basis.
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In silico characterization of the novel SDR42E1 as a potential vitamin D modulator – April 2024

J of Steroid Biochemistry and Molecular Biology Vol 238, April 2024, https://doi.org/10.1016/j.jsbmb.2023.106447 PDF is behind a paywall
Nagham Nafiz Hendi a, Georges Nemer a b

Highlights

• SDR42E1 protein demonstrates a strong affinity for key vitamin D intermediates, notably 8-dehydrocholesterol.
• The evolutionary conservation of hydrophobic interactions between vitamin D and SDR42E1 emphasizes its crucial role in regulating vitamin D skin synthesis.

The short-chain dehydrogenase/reductase (SDR) superfamily encompasses enzymes that play essential roles in the metabolism of steroid hormones and lipids. Despite an enigmatic function, recent genetic studies have linked the novel SDR 42 extended-1 (SDR42E1) gene to 25-hydroxyvitamin D levels. This study investigated the potential SDR42E1 functions and interactions with vitamin D using bioinformatics and molecular docking studies. Phylogenetic analysis unveiled that the nucleotide sequences of human SDR42E1 exhibit high evolutionary conservation across nematodes and fruit flies. Molecular docking analysis identified strong binding affinities between SDR42E1 and its orthologs with vitamin D3 and essential precursors, 8-dehydrocholesterol, followed by 7-dehydrocholesterol and 25-hydroxyvitamin D. The hydrophobic interactions observed between the protein residues and vitamin D compounds supported the predicted transmembrane localization of SDR42E1. Our investigation provides valuable insights into the potential role of SDR42E1 in skin vitamin D biosynthesis throughout species. This provides the foundation for future research and development of targeted therapies for vitamin D deficiency and related health conditions.

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Genome-Wide Association Study of Vitamin D Deficiency in the Middle East With a Relevant Characterization of the Novel SDR42E1 Gene – April 2023

 ProQuest Dissertations & Theses,  2023. 30420472.
Hendi, Nagham Nafiz Ahmad.   Hamad Bin Khalifa University (Qatar)
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VitaminDWiki - Genetics chart shows the vitamin D genes

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VitaminDWiki - Middle East and Vitamin D contains

154 items in Middle East category
see also Overview Middle East and vitamin D

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Vitamin D levels are very low in the Middle East

Vitamin D genes vary with UVB in Europe, Africa, Asia – March 2020
Vitamin D levels from lowest to highest: Middle East, China. India, S EU. N EU – Dec 2019
International Conference on Vitamin D Deficiency – 8th Abu Dhabi – April 2019
Top 5 health concerns of women in UAE (all have been treated by Vitamin D) – April 2018
Vitamin D given to ALL high schools girls in Iran – 75 percent deficiency dropped to 6 percent – April 2016
Turkey gave 400 IU vitamin D to all infants and reduced Rickets by 60X - 2011