Thursday, January 08, 2009

SNIP associated with statin related myopathy

The August 21,2008 issue of the NEJM published an interesting paper entitled " SLCO1B1 and statin-induced myopathy" by the Search Collaborative Group.

They found a SNIP (Single nucleotide polymorphism) that is "strongly associated with an increased risk of statin-induced myopathy" .They used 300,000 markers -a genome wide scan- and ferreted out a SNIP on chromosome 12 that is related to the liver uptake of statins (I am not sure if this is all or just some statins) and a certain allele was associated with a odds ratio of an impressive 16.9.

This beats the heck out of the relative risk in the range of 1 to 2 that from time to time stirs up inappropriate concern and sophomoric media attention derived from a quick and dirty case control study.

The primary data source was from the SEARCH trial of over 12,000 participants from the UK who had a history of myocardial infarction and received either 80 mg or 20 mg of simvastatin daily. Definite myopathy (CK greater than 10 times the upper limit of normal plus muscle pain occurred in 49 of the 6031 subjects receiving the 80 mg dose, with 2 occurring in the 20 mg dose group. The odds ratio was 16.9 for those who were homozygous for the C allele. 60 % of the simvastatin associated myopathy cases were attributed to the gene variation. For the other 40% other cause or causes remain undetected. In those patients with myopathy using a high throughput technique about half a million genetic markers were screened. The results were replicated when applied to subjects from the Heart Protection trial with myopathy and an elevated but less impressive relative risk of 2.6 was demonstrated.

Note that presence of this particular mutation does not mean the patient will necessarily develop a myopathy and a number of patients without the SNIP will develop myopathy. So why is that? The physicist John Wheeler is quoted as saying:

"As the island of knowledge grows so does the shore of our ignorance."

but at least we seem to be making progress and the occurrence of myopathy related to statin use is now a bit less random and a bit more deterministic but we still have not squeezed all the randomness out.

In this age of the mega randomized trials and the chanting of treat- to- goal based on group data we might want to sit back sit back and remember the ecologic fallacy , what seems true for the group may not be true for any given individual.

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