cyp2d6 results...need help interpreting

chemo072 · January 2008

Hi all, I know there's info like this in the archives but I'm tired and need help from those with longer memories who remember where to find the info....

I know that there's a range of definitions of Intermediate, and I wonder if I fall into the high-functioning intermediate or the low-functioning-closer-to-poor-metabolizer side of intermediate. Kashcraft or Tender, are you out there?

I haven't talked to my onc. yet, got tired of waiting for him to call and asked to have the results faxed to me.

Here's what my test results say:

"Predicted Phenotype: Intermed(iate)

One non-functional allelle was detected. This genotype is consistent with an intermediate metabolizer phenotype for CYP2D6, indicating a potential for adverse drug reactions or failure to respond." (BTW, what IS an allelle, a phenotype or a genotype? I realize I don't know what these things ARE.)

"In addition, a promoter region variant was detected, consistent with the *2 allelle. Although this variant may affect expression it is considered a functional allelle." (What is a "promoter region"?)

..... (there's info on background of why to test for cyp2d6 etc., definitions of variants etc.)

at the very end, on page 2, it says:

"Variant 1: *5

Variant 2: *2A."

And when I run the GeneMedRx drug interaction chart as an intermediate metabolizer, I get different results. For instance, having tamoxifen in my system INCREASES the amount of ibuprofen in my system, which could explain why ibuprofen of all things was laying me flat. I'd take two and almost pass out...no longer, I feel like the tamoxifen is out of my system by now. It's been 2 months. And I DID have SEs from it, so it had to be getting metabolized somehow. That joint achiness was terrible.

I'm kicking myself for not having pressed my onc. to test more enzyme pathways...the GeneMedRx tool lists 2C9 as related to tamox. metabolism as well, and studies in pubmed list 2C19. Even if they're minor pathways, I'd like to know if those pathways are even open for me.

Ah well, a complicated world. But good - I've had over-reactions to meds for years, always needed super small doses....so this is sort of validating that way actually. Can't wait to hear what my onc. finds out and decides!

NativeMainer · January 2008

An allele is one of any 2 genes. For instance, if a certain gene has 2 X alleles (XX) the person is a female, if the gene has one X and one Y allele (XY) the person is a male.

Genotype is the genetic makeup of a person. It's the summary af the 2 allelles in a particular gene. Phenotype is the visible expression of the genotype. Using the same example, female genotype is XX, female phenotype is uterus, ovaries, breasts, wider hips, no Adam's apple, higher voice, smaller size. Male genotype is XY, male phenotype is penis, testicles. narrower hips, Adam's apple, lower voice, larger size.

Applying this to CYP2D6: Your genotype is one functional allelle and one non-functional allelle. Also, there is a variation in that part of the gene that encourages proper function (a "promoter" region) of the enzymes the gene makes. This makes your genotype "intermediate." Your phenotype, the expression of your genotype, is probably a higher metabolizer because of the promoter region variation.

Hope this helps.

chemo072 · January 2008

Native Mainer - it does help, thank you.

The *5 allele is referred to some places as the "del gene" variant, which as I read it may mean that it can delete the CYP2D6 gene. Which I must be misunderstanding, because it seems strange. However, it consistently shows up as nonfunctional, meaning no enzyme activity.

Then the whole promoter region gives me pause, because that does seemslike it'd be more active than normal, so I wonder if the two variants sort of cancel each other out, but the reality is probably not that as it's all very complicated.

cyp2d6 results...need help interpreting

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