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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

in Visio for 2023


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


24+ VitaminDWiki pages with CYP2R1 in title

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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

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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.

Attached files

ID Name Comment Uploaded Size Downloads
19196 CYP2R1 Stroke.jpg admin 10 Feb, 2023 128.62 Kb 410
19195 CYP2R1 preprint.pdf admin 10 Feb, 2023 433.93 Kb 197