Panaceia or Hygeia

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Archive for April, 2016

98% of very high cholesterol is not caused by mutations in the genetic code, another blow to the hype of the genome sequencing industry. 

Posted by Colin Rose on April 5, 2016

For more than 30 years  the mantra of the cholesterol industry has held that “high cholesterol” in the general population is caused by a genetic abnormality which must be “treated” with a drug, usually a statin, because lifestyle change would be largely futile. There was great hope that by sequencing the genome we could find a coding gene that would give us the key to eliminating atherosclerosis, the cause of heart attacks. But a recent publication in The Journal of the American College of Cardiology shows that only 1.7% of very high cholesterol can be explained by mutation of genes known to code for proteins involved in cholesterol metabolism. So what is  going on?

Variables like the blood concentrations of many metabolites and the intercellular concentrations of gene controlled products like RNA and proteins are largely related to environmentally influenced variation in the expression of normal genes, not mutations of the genes themselves.

An example of a disease truly caused by an abnormal coding gene is sickle cell anemia which has long been known to be caused by a mutation of just one of the millions of base pairs in the DNA code with no significant environmental influence.

But less than 2% of our DNA is used to code for proteins that form skin, blood, muscle, etc. The other 98% of our DNA, what used to be called junk DNA, is composed of code that regulates the protein coding DNA and is very sensitive to environmental influences like diet, smoking, drugs, exercise, weather, air pollution, etc. How this non-coding DNA is influenced by the environment and how it controls the expression of coding DNA is very mysterious.  It will be a long time before we have a precise mathematical model of the thousands of self referential pathways involved in gene regulation. In the meanwhile we have pretty good evidence for which environments are healthy and that influencing gene expression in this manner is much more important than prescribing drugs to “treat” just one of the results of the alteration of gene expression like high cholesterol.

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