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Multiple Sclerosis risk increased due to genes - 22nd study – Aug 2017

Low-Frequency Synonymous Coding Variation in CYP2R1 Has Large Effects on Vitamin D Levels and Risk of Multiple Sclerosis

The American Journal of Human Genetics, Vol 101, # 2, 3 August 2017, Pages 227–238, https://doi.org/10.1016/j.ajhg.2017.06.014

  • CYP2R1 gene problem resulted in 1.4X increased risk of Multiple Sclerosis
  • The CYP2R1 gene works in parallel with the liver to semi-activate vitamin D
  • A Vitamin D test measures the amount of semi-activated vitamin D in the blood
  • Another gene, the Vitamin D Receptor (VDR), independently restricts how much Vitamin D actually gets to the cells
  • A poor VDR is independently associated with 3X ncreased risk of MS
  • Note: 33+ diseases are strongly associated with the Vitamin D Receptor
    • Perhaps a 5X increase in chance of getting MS if both CYPR1 and VDR are bad

Genetics category listing contains the following

248 articles in the Genetics category

see also 311 articles in Vitamin D Receptor, 116 articles in Vitamin D Binding Protein

Vitamin D blood test misses a lot
Blood Test Misses a lot (VDW 3439)

  • Snapshot of the literature by VitaminDWiki - (subject to many future developments)
  • Vitamin D from coming from tissues (vs blood) was speculated to be 50% in 2014, andi in 2017 is speculated to be 90%
  • Note: Good results from a blood test (> 40 ng) does not mean that a good amount of Vitamin D actually gets to cells
  • A Vitamin D test in cells appears feasible (personal communication)
    However test results would vary in each tissue due to multiple genes
  • Good clues that Vitamin D is being restricted from getting to the cells
    1) A vitamin D-related health problem runs in the family
       especially if it is one of 51+ diseases related to Vitamin D Receptor
    2) Slightly increasing Vitamin D show benefits (even if conventional Vitamin D test shows an increase)
    3) Vitamin D Receptor test (<$30) scores are difficult to understand in 2016
        easier to understand the VDR 23andMe test results analyzed by FoundMyFitness in 2018
    4) Back Pain
        probably want at least 2 clues before taking adding vitamin D, Omega-3, Magnesium, Resveratrol, etc
          The founder of VitaminDWiki took action with clues #3&4

19+ studies of MS and Genetics
   (and 6+ studies with VDR, below) :

6+ studies of MS and Vitamin D Receptor:

Despoina Manousaki1, 2, 49, Tom Dudding3, 49, Simon Haworth3, 49, Yi-Hsiang Hsu4, 5, 6, 49, Ching-Ti Liu7, 49, Carolina Medina-Gómez8, 9, 10, 49, Trudy Voortman9, 10, 49, Nathalie van der Velde8, 11, 49, Håkan Melhus12, 49,

Vitamin D insufficiency is common, correctable, and influenced by genetic factors, and it has been associated with risk of several diseases. We sought to identify low-frequency genetic variants that strongly increase the risk of vitamin D insufficiency and tested their effect on risk of multiple sclerosis, a disease influenced by low vitamin D concentrations. We used whole-genome sequencing data from 2,619 individuals through the UK10K program and deep-imputation data from 39,655 individuals genotyped genome-wide. Meta-analysis of the summary statistics from 19 cohorts identified in CYP2R1 the low-frequency (minor allele frequency = 2.5%) synonymous coding variant g.14900931G>A (p.Asp120Asp) (rs117913124[A]), which conferred a large effect on 25-hydroxyvitamin D (25OHD) levels (−0.43 SD of standardized natural log-transformed 25OHD per A allele; p value = 1.5 × 10−88). The effect on 25OHD was four times larger and independent of the effect of a previously described common variant near CYP2R1.

By analyzing 8,711 individuals, we showed that heterozygote carriers of this low-frequency variant have an increased risk of vitamin D insufficiency (odds ratio [OR] = 2.2, 95% confidence interval [CI] = 1.78–2.78, p = 1.26 × 10−12).

Individuals carrying one copy of this variant also had increased odds of multiple sclerosis (OR = 1.4, 95% CI = 1.19–1.64, p = 2.63 × 10−5) in a sample of 5,927 case and 5,599 control subjects. In conclusion, we describe a low-frequency CYP2R1 coding variant that exerts the largest effect upon 25OHD levels identified to date in the general European population and implicates vitamin D in the etiology of multiple sclerosis.

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Created by admin. Last Modification: Wednesday November 14, 2018 03:35:46 GMT-0000 by admin. (Version 12)

Attached files

ID Name Comment Uploaded Size Downloads
8254 CYP2R1 MS.pdf p admin 04 Aug, 2017 20:56 1.50 Mb 153
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