Kickas.org Forums Ankylosing Spondylitis General Discussion #1 AS Web Support Group Yet another genetic link, CYP2D6

a discussion in another thread brought up the connection between CYP2D6 polymorphisms (common mutations in this P450 - liver enzyme that processes a number of drugs including codeine and tramadol) and the spondylarthropathies:

http://hmg.oxfordjournals.org/content/9/11/1563.full

other articles too but required subscription:

section 5.3 of this paper looks interesting in this regard:

Genetics of the Spondyloarthropathies

so, if you are HLAB27 negative, have a spondy, and have had issues with either codeine and/or tramadol having little to no effect, this could be the connection. i wonder if this is the link for me, have known since my 20s that codeine has no pain relieving effects for me, just puts me out, so have suspected that i have a mutation in this gene. some googling indicated that this gene can be genetically tested for. wonder if i should request this, will ask doctors.

another link, see table 4:

http://emedicine.medscape.com/article/332945-overview

another interesting link:

http://www.ncbi.nlm.nih.gov/omim/124030

paragraph pertinent to AS:

Other Disease Associations

Brown et al. (2000) performed a linkage study of chromosome 22 in 200 families with ankylosing spondylitis (AS; 106300)-affected sib pairs. While homozygosity for PM alleles was found to be associated with AS, heterozygosity for the most frequent PM allele (CYP2D6*4) was not associated with increased susceptibility to AS. Significant within-family association of CYP2D6*4 alleles and AS was demonstrated. Weak linkage was also demonstrated between CYP2D6 and AS. The authors hypothesized that altered metabolism of a natural toxin or antigen by the CYP2D6 gene may increase susceptibility to AS.

Interesting, Sue. Thanks for this!

Warm hugs,

thanks kat!

think i've found this particularly interesting because:

1. i am HLAB27 negative

2. i know i don't process codeine properly and thus have suspected for years that i had issues with my CYP2D6.

3. seems that i'm undiff spondy vs AS (unless AS presents itself later as it does with many) so have often wondered if HLAB27 is a good marker for AS (90-95% of ASers have the gene) and a poor marker for undiff spondy (20-25% have have the gene), then what if anything would be a better marker for undiff spondy.