[olsen]

Ramagopalan SV et al. Rare variants in the CYP27B1 gene are associated with multiple sclerosis Ann Neurol 2011 Dec 70:881.

http://neurology.jwatch.org/cgi/content/full/2012/117/1

Mutations that lead to altered vitamin D activation are identified as rare variants in familial MS.
To identify rare alleles...), investigators conducted genetic analyses in more than 12,000 people from a cohort of more than 30,000 families, including 43 families that had four or more individuals with MS.
... identified a single nucleotide polymorphism within the CYP27B1 gene that was present in all four individuals with MS from one genotyped family and was incompletely penetrant. Additional CYP27B1 mutations were found within 3046 trios of parents with an affected child and in 422 parent–affected sibling pairs. The CYP27B1 mutation frequency was 0.9% in MS patients compared with 0.0% in 1873 healthy controls.

CYP27B1 encodes the enzyme that converts 25-hydroxyvitamin D to biologically active vitamin D.

Comment: ... refined the search by focusing on strongly familial forms of MS. By identifying a rare mutation in a gene associated with vitamin D, this work contributes to understanding a potential mechanism underlying the associations between MS and serum vitamin D level (JW Neurol May 3 2011), ultraviolet exposure with latitude (JW Neurol Feb 7 2011), and late spring birth (BMJ 2005; 330:120). Trials of vitamin D supplementation in MS are now under way to determine whether this will alter relapse rates and magnetic resonance imaging lesions.



Abstract
OBJECTIVE:
To perform a 1-stage meta-analysis of genome-wide association studies (GWAS) of multiple sclerosis (MS) susceptibility and to explore functional consequences of new susceptibility loci.
METHODS:
We synthesized 7 MS GWAS. Each data set was imputed using HapMap phase II, and a per single nucleotide polymorphism (SNP) meta-analysis was performed across the 7 data sets. We explored RNA expression data using a quantitative trait analysis in peripheral blood mononuclear cells (PBMCs) of 228 subjects with demyelinating disease.
RESULTS:
We meta-analyzed 2,529,394 unique SNPs in 5,545 cases and 12,153 controls. We identified 3 novel susceptibility alleles: rs170934(T) at 3p24.1 (odds ratio [OR], 1.17; p = 1.6 × 10(-8)) near EOMES, rs2150702(G) in the second intron of MLANA on chromosome 9p24.1 (OR, 1.16; p = 3.3 × 10(-8)), and rs6718520(A) in an intergenic region on chromosome 2p21, with THADA as the nearest flanking gene (OR, 1.17; p = 3.4 × 10(-8)). The 3 new loci do not have a strong cis effect on RNA expression in PBMCs. Ten other susceptibility loci had a suggestive p < 1 × 10(-6) , some of these loci have evidence of association in other inflammatory diseases (ie, IL12B, TAGAP, PLEK, and ZMIZ1).
INTERPRETATION:
We have performed a meta-analysis of GWAS in MS that more than doubles the size of previous gene discovery efforts and highlights 3 novel MS susceptibility loci. These and additional loci with suggestive evidence of association are excellent candidates for further investigations to refine and validate their role in the genetic architecture of MS

http://www.ncbi.nlm.nih.gov/pubmed/22190364

[olsen]

http://ganymedes.lib.unideb.hu:8080/...g.2010.113.pdf


and the following:
http://wattle.well.ox.ac.uk/wtccc2/external/ms/

Multiple Sclerosis GWAS Browser
This site accompanies the article "Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis", The International Multiple Sclerosis Genetics Consortium (IMSGC) and the Wellcome Trust Case Control Consortium 2 (WTCCC2), Nature (2011). The data sources for this page are those described in the above article, and were current at the time of article preparation.
Overview. The plot on the left depicts regions of the human genome which have been found to be statistically associated with Multiple Sclerosis, as described in the above article.
http://wattle.well.ox.ac.uk/wtccc2/external/ms/

[lurkingforacure]

Originally Posted by olsen

http://ganymedes.lib.unideb.hu:8080/...g.2010.113.pdf


and the following:
http://wattle.well.ox.ac.uk/wtccc2/external/ms/

Multiple Sclerosis GWAS Browser
This site accompanies the article "Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis", The International Multiple Sclerosis Genetics Consortium (IMSGC) and the Wellcome Trust Case Control Consortium 2 (WTCCC2), Nature (2011). The data sources for this page are those described in the above article, and were current at the time of article preparation.
Overview. The plot on the left depicts regions of the human genome which have been found to be statistically associated with Multiple Sclerosis, as described in the above article.
http://wattle.well.ox.ac.uk/wtccc2/external/ms/

Wow, this is complex. There are a LOT more genes associated with MS than I ever imagined, so many, in fact, that I wonder how this info really helps us? Further, it is well known that MS significantly predominates in women, so I wonder why they left off the sex chromosome in their analysis.

I am thinking of Dr. Wahl and her diet/exercise program which sent her MS into remission. Wonder which of these genes she has, or whether it matters, really...as she said, she believes our DNA contains the wisdom to heal us.