(copied from previous posting on ""lipoproteins)
Genetics may prove to be the most important link btn statins and the development of neurodegenerative diseases. The directional movement of drugs across the membranes of organs for metabolization/detoxification frequently requires the action of uptake transporters. OATP-C (frequently presented in literature as the SLCO1B1 gene) represents the liver- specific transporter protein that facilitates the uptake of statins from the portal blood into the hepatocytes of the liver so that statins can be metabolized and excreted into the bile.

There are 2 studies often cited noting an association btn neighboring SNPs in the SLCO1B1 gene and severe myopathies/myalgias, and one study noting mutations in the COQ2 gene (which encodes an enzyme involved in coenzyme Q10 production) and myopathies. Most references to these studies usually contain disclaimers as to their significance/lack of confirmation. There are many other studies noting greatly affected pharmacokinetics of statins in relation to these polymorphisms, esp ones involving SLCO1B1 gene mutations, though most of these studies are published in Pharmacology Journals, not mainstream medical jrls. The 2 neighboring SNPs noted in the first study cited under heading "research reports" from 23aqnd me web site:
( SEARCH Collaborative Group et al. 2008 )
are present in a large % of the population: predicted occurrance for the first SNP (rs149056) in caucasian pop: 20% to24% of the population. Predicted occurrance for the second SNP noted ( rs4693596) is much lower, though still a factor given the millions of individuals who are taking statins: 4% to 8% of the caucasian population (the population studies providing these #'s were done on a caucasian scandinavian population.

Pharmacokinetic studies have noted in individuals who posses one of the SNPs in the SLCO1B1 gene )TT genotype), AUC of statins levels were 200% to 400% ABOVE NORMAL.

Journal N Engl J Med

Marker rs4149056
Thius study included 2 groups of patients taking statins after sufferring a heart attack: 85 who developed myopathies and 90 who did not. Simvastatin 80 mgm/d was the drug each group was taking. Findings: having one C at rs4149056 (a SNP in the SLCO1B1 gene) increased one's odds 4.5 times of having myopathy over those with TT genotype. THose individuals with CC genotype had increased odds for myopathy of 17 times that compared to individuals with the TT genotype. There were increased odds of developing myopathy in individuals taking simvastatin at 40 mgm/d, though the effects were "less extreme".

CC Greatly increased odds of myopathy while on simvastatin (odds of developing myopathy 17X's those with TT genotype)
CT Substantially increased odds of myopathy while on simvastatin(odds of developing myopathy 4.5 X's those with TT)
TT Typical odds of myopathy while on simvastatin.

Citations
SEARCH Collaborative Group et al. (2008) . “SLCO1B1 variants and statin-induced myopathy--a genomewide study.” N Engl J Med 359(8):789-99.

STUDY #2:

Marker rs4693596
Study compared one group of 133 patients who developed myopathy while taking a statin to a group of 158 patients who did not develop myopathy while on a statin. (different statins were taken at varying doses in both groups) The study reported an association btn myopathy and a SNP in the COQ2 gene. This gene encodes an enzyme responsible for ultimate production of ubiquinone or coenzyme Q10. Those individuals with CC genotype for this marker, rs4693596, had more than 2X'x the odds of having myopathy while on a statin, than those with a CT or TT genotype.
CC Moderately higher odds of myopathy while on statin therapy (odds of developing myopathy 2X's those with CT or TT genotype)
CT Typical odds of myopathy while on statin therapy.
TT Typical odds of myopathy while on statin therapy.

Oh J et al. (2007) . “Genetic determinants of statin intolerance.” Lipids Health Dis 6:7

There have been no studies looking at mutations in either of these genes (SLCO1B1 and COQ2) and the association to neurodegenerative diseases. There are reports of increased plasma statin plasma levels for individuals with the SLCO1B1 mutations, indicating statins are not being detoxified. There is a critical level above which statin toxicities occur. For the lucky ones, severe myalgias and myopathies develop, necessitating discontinuance of the drug. For those who do not suffer from myalgias, the drug is taken as prescribed, and I suspect neurodegenerative disease results.

23andme offers DNA partial profiling; individuals with Parkinson's are able to obtain this test for $25; I am unsure if others with neurodegenerative diseases are provided a savings for the test. This profiling includes info re: SNPs in SLCO1B1 as well as the CoQ gene.
Guess question #3 could be: who has a genetic mutation in either of these genes?

Thank you Mary!

I'll have to get the full version.

Best regards,
Nemesis