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New Variants of the Cytochrome P450 2R1 (CYP2R1) Gene in Individuals with Severe Vitamin D-Activating Enzyme 25(OH)D Deficiency
- Source :
- Biomolecules, Biomolecules, Vol 11, Iss 1867, p 1867 (2021), Biomolecules; Volume 11; Issue 12; Pages: 1867
- Publication Year :
- 2021
- Publisher :
- MDPI, 2021.
-
Abstract
- Background: Vitamin D is a fat-soluble cholesterol derivative found in two forms, vitamin D2, and vitamin D3. Cytochrome P450 2R1 (CYP2R1) encoded by the CYP2R1 gene is the major hydroxylase that activates vitamin D by catalyzing the formation of 25-hydroxyvitamin D (25(OH)D). Methods: We collected 89 (100%) subjects, 46 of which (51.69%) had a documented severe deficiency of 25(OH)D (30 ng/mL). We performed Sanger sequencing of three selected fragments of the CYP2R1 gene (Ch11: 14878000–14878499; Ch11: 14880058–14880883 and Ch11: 14885321–14886113) that affect the binding of substrates to this enzyme and analyzed the possible involvement of genetic variation in these regions with an increased risk of vitamin D deficiency in healthy Polish individuals. Results: Two substitutions were found within the three fragments. Bioinformatic analysis suggested that one of these (NC_000011.10: g.14878291G>A) may influence the structure and function of CYP2R1. Conclusions: Variant NC_000011.10: g.14878291G>A may have a perturbing effect on heme binding in the active site of CYP2R1 and on the function of 25-hydroxylase and probably affects the concentration of 25(OH)D in vivo. We intend to perform functional verification in a larger patient population to confirm and extend these results.
- Subjects :
- Adult
Male
vitamin D
metabolism of vitamin D or its analogs
cytochrome P450
CYP2R1
25-hydroxylase
Binding Sites
Sequence Analysis, DNA
Vitamin D Deficiency
Biochemistry
Microbiology
QR1-502
Article
Young Adult
Amino Acid Substitution
Case-Control Studies
Cholestanetriol 26-Monooxygenase
Humans
Female
Cytochrome P450 Family 2
Molecular Biology
Subjects
Details
- Language :
- English
- ISSN :
- 2218273X
- Volume :
- 11
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- Biomolecules
- Accession number :
- edsair.doi.dedup.....8308f93755d98ae1f9a97fe529698ac2