@mariovitali - I'm trying to think of a good way to explain the relationship between SNPs and disease. I'm not a teacher, so it's not something I'm any good at. But since you don't have a couple hours per week to spare for a proper free introductory course online, here's my attempt:
SNPs (or more specifically alleles) are the basis of genes. Typically there are hundreds or thousands of them on each gene. The gene creates a protein. If there is a major change in that protein, it might function differently. That can result in too much or too little of the protein, or the protein being too effective or ineffective at doing its job, or no protein being created at all. When the protein is badly malfunctioning, that is when disease can result.
SNPs --> gene --> protein --> disease.
So SNPs can result in disease, but you can't take a shortcut straight from SNP --> disease. The SNP will only cause disease if it fundamentally alters the protein.
I think I see where you two are getting stuck.
It is not just:
SNPs --> gene --> protein --> disease
It is also:
SNPs --> gene --> protein --> increased risk of disease
For example, lets look at selenoprotein genes:
http://www.mdpi.com/2072-6643/7/5/3621/htm
Although epidemiological studies indicate that low Se intake is linked to increased risk for various chronic diseases, supplementation trials have given confusing outcomes, suggesting that additional genetic factors could affect the relationship between Se and health. Genetic data support this hypothesis, as risk for several chronic diseases, in particular cancer, was linked to a number of single nucleotide polymorphisms (SNP) altering Se metabolism, selenoprotein synthesis or activity. Interactions between SNPs in selenoprotein genes, SNPs in related molecular pathways and biomarkers of Se status were found to further modulate the genetic risk carried by the SNPs. Taken together, nutritional genomics approaches uncovered the potential implication of some selenoproteins as well as the influence of complex interactions between genetic variants and Se status in the aetiology of several chronic diseases.
So SNPs, in combination with poor diet,
may lead to disease. These genetic variants will mean some people might need much more selenium than others in order to not have a disease. It is not that say that a particular GPX2 SNP CAUSES disease, but it can increase the risk of disease. So far there are zero studies that have encompassed genetics, diet, and lifestyle in a way that can point to this. They are just too large and too difficult and they will never happen, so you will never have the proof you are looking for.
This was 100% true for me and my BTD and HLCS genes. If I get enough Biotin I do not have seb derm. At this point I cannot say that everyone who has Seb Derm has my genotype, or that everyone with my genotype will have seb derm, it depends on their diet and possibly some other genes that have to do with stress (MAOA). This is for each person to figure out. And this is where I think both you and Mario get it wrong. You keep looking for the "one thing" that will fix ME. There is no one thing, there is only one method to find out. That method is looking at our own genetics to look for clues (not proof) of what diet and supplements we might need to reduce our risk of disease and to cure our disease.
So what Mario is looking at are SNPs that might increase the risk of ME, not directly cause it.
Basically, it's not possible to guess that SNPs outside of exons are having any impact. We need proper research showing that those SNPs do or do not have an impact. If predicting is to be done, it's for the missense mutations (amino acid changes) or nonsense mutations (premature stops) in the exons, and there are valid ways in which to go about it. Some are simple, like the BLOSUM62 amino acid chart, and some programs evaluate dozens of factors regarding the amino acid, it's location, nearby amino acids, 3D modeling, etc. So this is also a far cry from guessing blindly.
I did the research, on myself, with my Biotin genes. And then some other people tried it, some with my SNPs, some without. I kept everything in my life the same (diet, stress, etc) and I only added and removed Biotin. If SNPs had no impact we would see no variation in response. But that variation in response was clearly evident. Notably that people without two BTD SNPs got headaches taking the Biotin and people without them did not. Is it worthy of a journal? No, but who cares? My seb derm is gone, so are a few others. I have done this for other SNPs as well. It was a matter of testing BASED on my genetics to see if SNPs were effecting cofactor use. You see this in the MTHFR gene, how the MTHFR gene with certain SNPs can increase activity when given enough FAD,
Understanding genetics is important, but understanding nutritional genomics is also important. Have you taken any classes in Nutritional Genomics? They might help broaden your understanding.
