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Not a Geneticist - But looking for assistance - please read - (Jul/13/2010 )

Hello everyone,

I found this message board when searching on google for information on epigenetics and methylation, after a theory was posted on a support group for people who have been physically damaged by the drug finasteride (propecia) even long after the drugs cessation. So far, traditional doctors have been unable to help 90% of the men with this issue.

I am posting to because it is theorized that the drug causes hypermethylation of the androgen receptor, causing partial androgen insensitivity in certain men who take it. Why this drug does this in certain men, I am unsure - but this is also a proposed side effect of the pharmaceutical accutaine (Isotretinoin), as mentioned in the paper below:

Epigenetic side-effects of common pharmaceuticals: a potential new field in medicine and pharmacology.
http://www.ncbi.nlm.nih.gov/pubmed/19501473

a quote from this paper is also of interest:

"methylation of the androgen receptor promoter CpG island is associated with loss of androgen receptor expression in prostate cancer cells. The demethylating agent 5-aza-2′ deoxycytidine induced a re-expression of AR RNA." http://www.ncbi.nlm.nih.gov/sites/pubmed/9850055.

My point of this post is: Is there any way to definitively test for hypermethylation of the AR - in any clinical setting? I know there are currently some demethylating agents in development, but of course these are useless unless hypermethylation has actually occured. If any scientist that may be reading this has interest in the study of pharmacoepigenomics and beleives they may be able to help, I would be truly thankful for any information regarding this issue. There are currently thousands of men suffering from the side effects of both accutane and finasteride, and assistance from the scientific community may be our only way to return to some level of normalcy.

Thank you for taking the time to read this, and feel free to ask any questions - on here or via email.

Golf

-golf17331-

There is certainly scope there golf and it is possible to test for hypermethylation of AR. The question is what biospecimens are available? Ideally you would want a tissue that is closest to the diseased tissue of interest. In this case I would imagine it is the scalp? It would be more contentious to use a surrogate tissue but it still could be done.

N

-methylnick-

methylnick on Jul 13 2010, 09:05 PM said:

There is certainly scope there golf and it is possible to test for hypermethylation of AR. The question is what biospecimens are available? Ideally you would want a tissue that is closest to the diseased tissue of interest. In this case I would imagine it is the scalp? It would be more contentious to use a surrogate tissue but it still could be done.

N


Based on the side effects from which the finasteride/accutane users exhibit, which is a lack of response to androgens (leading to an array of damaging effects) the sample would most likely be from genital or prostate tissue.

-golf17331-