CYP2R1 gene reduces response to Vitamin D - many studies

People with a poor CYP2R1 genes are poor Vitamin D responders
    Possible solution: take larger doses of Vitamin D

VitaminDWiki - Genetics chart shows the vitamin D genes

Genes and other reasons for poor blood response to Vitamin D supplementation

• Poor or no response to vitamin D was associated with poor genes (cystic fibrosis, 4 genes) Sept 2022

• Reasons for low response to vitamin D

• Autistics have half of the response to Vitamin D – RCT Oct 2018

• Poor CYP2R1 gene reduces blood response to Vitamin D supplementation – Aug 2019

• Poor Vitamin D response 4X more likely if poor Vitamin D binding proteins - July 2019

• Vitamin D Nutrigenomics - High, Medium, and Low Responders - March 2019

• Vitamin D non-responders may have one or more poor genes: GC, LIPC, CYP24A1, and PDE3B – Oct 2022

CYP2R1 problems: 1 in 12 in the tropics, 1 in 143 African-Americans, 1 in 333 Caucasians

Heterozygous carriers of CYP2R1 variants with decreased 25-hydroxylase activity are more common but still relatively rare in Western populations:

These heterozygous carriers have a 30–60% reduction in circulating 25(OH)D and show diminished response to vitamin D supplementation. They may benefit from calcidiol but can often achieve adequate levels with higher doses of vitamin D3.[^5]

More information and references at Perplexity AI

24+ VitaminDWiki pages with CYP2R1 in title

This list is automatically updated

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CYP2R1 was the gene most associated with increased risk of Ischemic Stroke - Feb 2023

Whole-Exome Sequencing Analyses Support a Role of Vitamin D Metabolism in Ischemic Stroke

Stroke . 2023 Feb 10. doi: 10.1161/STROKEAHA.122.040883 PDF of Preprint

Yuhan Xie # 1, Julián N Acosta # 2, Yixuan Ye 3, Zachariah S Demarais 4, Carolyn J Conlon 4, Ming Chen 1, Hongyu Zhao 1 3, Guido J Falcone 2

Background: Ischemic stroke (IS) is a highly heritable trait, and genome-wide association studies have identified several commonly occurring susceptibility risk loci for this condition. However, there are limited data on the contribution of rare genetic variation to IS.

Methods: We conducted an exome-wide study using whole-exome sequencing data from 152 058 UK Biobank participants , including 1777 IS cases. We performed single-variant analyses for rare variants and gene-based analyses for loss-of-function and deleterious missense rare variants. We validated these results through

• (1) gene-based testing using summary statistics from MEGASTROKE-a genome-wide association study of IS that included 67 162 IS cases and 454 450 controls,

• (2) gene-based testing using individual-level data from 1706 IS survivors, including 142 recurrent IS cases, enrolled in the VISP trial (Vitamin Intervention for Stroke Prevention); and

• (3) gene-based testing against neuroimaging phenotypes related to cerebrovascular disease using summary-level data from 42,310 UK Biobank participants with available magnetic resonance imaging data.

Results: In single-variant association analyses, none of the evaluated variants were associated with IS at genome-wide significance levels (P<5×10-8). In the gene-based analysis focused on loss-of-function and deleterious missense variants, rare genetic variation at CYP2R1 was significantly associated with IS risk (P=2.6×10-6), exceeding the Bonferroni-corrected threshold for 16 074 tests (P<3.1×10-6). Validations analyses indicated that CYP2R1 was associated with IS risk in MEGASTROKE (gene-based test, P=0.003), with IS recurrence in the VISP trial (gene-based test, P=0.001) and with neuroimaging traits (white matter hyperintensity, mean diffusivity, and fractional anisotropy) in the UK Biobank neuroimaging study (all gene-based tests, P<0.05).

Conclusions: Because CYP2R1 plays an important role in vitamin D metabolism and existing observational evidence suggests an association between vitamin D levels and cerebrovascular disease, our results support a role of this pathway in the occurrence of IS.