Genetic Susceptibility to Statin Drugs


Duane Graveline MD - Updated January 2009

"Taking a new medicine is the start of a new experiment." Nowhere is this truer than with the statin class of drugs. Although the majority of statin users appear to do well, the collateral damage of this class of drug is such that diverse symptoms, reflecting multiple metabolic pathways, can be expected.

Glial cell inhibition of cholesterol synthesis appears to be the cause for such cognitive manifestations as amnesia, confusion, disorientation and forgetfulness. Dolichol inhibition is directly tied to altered neuropeptide synthesis and many behavioral side effects such as aggressiveness, depression and irritability. CoQ10 inhibition seems directly tied to statin associated myopathies, neuropathies and rhabdomyolysis.

Now it is suspected that some people may have a genetic susceptibility to statin-induced problems. Special genetic susceptibility may explain not only much of the statin associated rhabdomyolysis but also the curious pattern of persistent myopathy, often following only a short course of statins. Since susceptibility testing of this type is not yet available, there is no way to identify those who are susceptible until the damage is done.

Such concerns document the validity of the opening statement. Every statin user is the start of an experiment. One can hardly justify this class of drugs for wide-scale use as in primary prevention and over the counter distribution (as in the U.K.) when the completely unpredictable end-point may be rhabdomyolysis death or permanent myopathic debility.

One of these genetically determined enzymatic conditions is carnitine palmitoyltransferase (CPT) II deficiency. CPT I and II are enzymes found on different membranes within the mitochondrion, those busy factories within each of our cells responsible for the production of (ATP) energy. CPT I and II together with other transporters, such as carnitine, are responsible for bringing lipids into mitochondria for the ultimate production of  ATP.

Produced in each of our body's million's of cells, mitochondrial ATP is our body's sole source of energy. Deficiency of this class of enzymes is characterized by unusual muscle pain and stiffness after exercise or work.

The process of energy production in muscle cells is dependant on a complex interplay of other substances, such as coenzyme Q10 or CoQ10, which aides in the transport of electrons in an enzyme system known  as the respiratory chain. When any of these substances are insufficient, myopathy may result. Mutations can occur in any of the genes encoding these proteins causing major interruptions of energy production. 

Georgirene Vladutiu PhD, of the Robert Guthrie Biochemical Genetics Laboratory, reports that, "A study is underway at the University at Buffalo to pursue the possible role genetic factors may play in increasing susceptibility to statin myopathies. There is preliminary evidence that certain underlying muscle disorders may play a role in conferring increased susceptibility to statin-induced myopathies."

Duane Graveline MD MPH
Former USAF Flight Surgeon
Former NASA Astronaut
Retired Family Doctor

 


Books From Amazon

The Dark Side of Statins
The Statin Damage Crisis
Cholesterol is Not the Culprit
Statin Drugs Side Effects
Lipitor, Thief of Memory


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