In this study we
investigated the relationship between melatonin pathway and MS in a
high-risk Finnish population by studying the single nucleotide
polymorphisms (SNPs) in the genes coding for critical enzymes and
receptors involved in the melatonin pathway.
A total of 590 subjects (193 MSers and 397 healthy controls) were genotyped for seven SNPs in four genes including tryptophan hydroxylases
(TPH)1 and 2, arylalkylamine N-acetyltransferase (AANAT) and
http://ars.els-cdn.com/content/image/1-s2.0-S152166161100163X-gr1.jpg1B
(MTNR1B). An overrepresentation of T allele carriers of a functional
polymorphism (G-703T, rs4570625) in the promoter region of TPH2 gene was
observed in the progressive MS subtypes. The haplotype
rs4570625-rs10506645TT of TPH2 gene was associated with the risk of
severe disability in primary progressive MS (PPMS), while haplotype
rs4570625-rs10506645TC appeared to be protective against disability in
secondary progressive MS (SPMS).
In the MTNR1B gene, the
haplotype rs10830963-rs4753426GC was associated with the risk of SPMS,
whereas another haplotype rs10830963-rs4753426GT showed an association
with the risk of PPMS. These data showing the association of
polymorphisms in the TPH2 and MTNR1B genes with the progressive subtypes
of MS and disability suggest dysregulation in melatonin pathway.
Melatonin pathway seems to be involved in disease progression, and
therefore its potential effects in overcoming MS-related
neurodegeneration may be worth evaluating in future clinical trials.
Melatonin levels varies during the daily. It works by stimulating the melatonin receptor.This project has look at single nucleotide polymorphisms
and found some that seem to be associated with the development of
progressive MS. These are variations in the gene with changes in one of
the four nucleotides e.g. T = thymidine, G = guanine C = cytosine,
A=adenosine. G-703Trs4570625 indicates a switch of thymidine at position
703 of the gene SNP rs4570625 to guanine in the promoter (the bit
before the coding sequence of the gene) which drives expression of the
gene product.
How melatonin influences MS is unknown, there may be influences on sleep patterns
and there is experimental evidence for it to be an immune
modulator...this will be further impetus for Prof H to get Project M off
the ground.
I'm half Finnish from my mother's side, does that make it more likely for me to have had MS? I know that's not the point of the story, but I'm just curious.
ReplyDeleteDoes this also have anything to do with vit D deficiancy?
ReplyDeleteDear Matt
ReplyDeleteMaybe..half your genes come from your mum and some of them would therefore come from you ancestors. Some gene variants are found in certain populations I do not know how common this gene variant is in non-Finns, but remember no one gene makes MS, it is the combination of many gene variants that give small increases in risk of developing MS.
Does this also have anything to do with vit D deficiancy?
ReplyDeleteNot that I know off but there are some papers on link between vitamin D and melatonin and biological effects