Not sure if this belongs here, but have any of you guys had the DNA test for pharmaceutical issues? I just had it done, and discovered that I have issues with tons of meds, that thankfully, I haven’t tried. And I found out why codeine has no effect on me.
I have never even heard of this but that sounds really interesting. Can you give any more details on it, such as what it is, what it costs, what it tests for? Thanks
I got it through a company called GeneSight Psychotropic. I’ve got a shrink for ADD recently, just to see what’s changed both in me and in treatment. He wanted this right off the bat before considering any srcips or anythin. The company started off dealing with MTHFR stuff but is now doing a “Combinatorial Pharmacogenomic Test”. It is apparently usually covered by insurance, but they have pragrams to cut cost as well, and I think it’s only $300 anyway. I found out all kinds of stuff based on my genome. Like antipsychotics wouldn’t do anything to me either, and SSRI’s would be a really huge mistake.
That looks interesting. I don’t really take prescription meds at all, other than albuterol as needed. It would be really cool if someone designed something like this for AAS.
Thanks for sharing this information. NIce summary here along with some interesting examples near the bottom based on our knowledge of drug metabolism today. Would be nice to have a screen for AAS but probably not much of a market since they aren’t prescribed like SSRIs and lipid medications and opioids.
Also, nice review of the commercial products out there as of July 2020:
Take a look at OneOme RightMed Pharmacogenomic Test.
Also, maybe an interesting one for the AAS crowd:
Beta adrenergic receptor genotyping (ADRB2) for treatment-resistant asthma
ADRB2 (beta adrenergic receptor genotyping) is a genetic test used for asthma patients with poor symptom control. The target for beta2-agonist asthma medication is the B2-adrenergic receptor. The gene for the B2-adrengergic receptor is ADRB2. It is believed that a variation at one location of this gene may predict therapeutic responses to beta2-agonists. The Arg/Arg homozygous genotype at amino acid position 15 may indicate a need for a change in medication.
The textbook Cleveland Clinic: Current Clinical Medicine (2010) states that, in the presence of a polymorphism, the acute bronchodilator response to a β agonist, or protection from a bronchoconstrictor, may be affected. Studies indicate that in patients with Arg16Arg variant, the resulting β2-adrenergic receptor is resistant to endogenous circulating catecholamines (i.e., receptor density and integrity are preserved), with a subsequent ability to produce an acute bronchodilator response to an agonist). There are conflicting data regarding whether Arg/Arg homozygotes are prone to experience reflex morbidity with inhaled LABA, but the weight of evidence, particularly from more-recent studies, indicates that response to LABA when used in combination with ICS does not vary based on β2-adrenergic genotypes at codon 16.
In 2010, Bleecker and colleagues examined whether the response to salmeterol alone or in combination with an inhaled corticosteroid is influenced by beta- receptor polymorphisms. Subjects using only as-needed albuterol were screened and completed two sequential open-label run-in periods (8 wk on as-needed albuterol; 8 wk on as-needed ipratropium). Five hundred forty-four subjects were randomized by Arg16Gly genotype to salmeterol alone or with fluticasone propionate for 16 weeks. Change from baseline in morning peak expiratory flow was the primary endpoint. Lung function responses were sustained over treatment and no statistically significant changes from baseline between genotypes within treatments were observed. Overall mean changes in morning peak flow for salmeterol with fluticasone propionate were 32.6 L/min (Arg/Arg vs. Gly/Gly, 95% confidence interval [CI], -6.3, 22.1), 25.9 L/min (Arg/Arg vs. Arg/Gly, 95% CI, -7.1, 21.3), and 24.9 L/min (Arg/Gly vs. Gly/Gly, 95% CI, -13.0, 14.6), and for salmeterol alone were 19.4 L/min (Arg/Arg vs. Gly/Gly, 95% CI, -1.7, 21.4), 24.6 L/min (Arg/Arg vs. Arg/Gly, 95% CI, -13.0, 10.6), and 12.4 L/min (Arg/Gly vs. Gly/Gly, 95% CI, -0.2, 22.3) for Arg/Arg, Arg/Gly, and Gly/Gly genotypes, respectively. Other measures of asthma control showed similar responses. The results showed no evidence of a pharmacogenetic effect of beta-receptor variation on salmeterol response.
Basu and colleagues (2009) investigated whether the presence of Arg16 allele of the adrenergic beta(2)-receptor agonist gene (ADRB2) predisposed to exacerbations in young asthmatic patients taking regular salmeterol. Arg/Gly status at position 16 of ADRB2 was assessed in 1182 asthmatic patients. Asthma exacerbations, use of beta-agonists and other medications over the previous 6 months, and lung function were also studied. An increased risk of exacerbations per copy of he Arg16 allele was observed in asthmatic patients, regardless of treatment regimen (odds ratio [OR], 1.30; 95% CI, 1.09-1.55; P = .003). This appeared to be largely due to exposure to beta(2)-agonists because the risk of exacerbations observed in patients with the Arg16 allele was only observed in those receiving daily inhaled long- or short-acting beta(2)-agonist treatment (OR, 1.64; 95% CI, 1.22-2.20; P = .001). In contrast, there was no genotypic risk for exacerbations in patients using inhaled beta(2)-agonists less than once a day (OR, 1.08; 95% CI, 0.85-1.36; P = .525). The Arg16 genotype-associated risk for exacerbations was significantly different in those exposed to beta(2)-agonists daily versus those that were not (test for interaction, P = .022). The authors concluded that Arg16 genotype of ADRB2 was associated with exacerbations in asthmatic children and young adults exposed daily to beta(2)-agonists, regardless of whether the exposure is to albuterol or long-acting agonists, such as salmeterol.
In a 2008 article, Martin and associates evaluated the influence of single nucleotide polymorphisms in the beta(2)-adrenoceptor gene, on the response to inhaled beta(2)-agonists in children with acute asthma. One hundred and forty-eight children with acute asthma were recruited and genotyped for beta(2)Arg16Gly and beta(2)Gln27Glu. For Gln27Glu, individuals Gln27Gln took longest to stretch out to 1, 2 and 4 hourly beta(2)-agonists, followed by heterozygotes who were intermediate and Glu27Glu who responded most rapidly (1 hourly: 2.6 hr vs. 2.0 vs. 1.4, p = 0.02; 2 hourly: 10.6 hr vs. 10.7 vs. 6.8, p = 0.07; 4 hourly: 29.8 hr vs. 28.5 vs. 24.3, p = 0.30). The authors reported that the ability to prospectively identify children who respond less effectively to beta (2)-agonists during an acute asthma attack has the potential to allow the generation of genotype-specific treatment pathways.
In 2008, Giubergia et al assessed the frequency of beta2-adrenergic receptor (beta2-AR) polymorphisms in asthmatic children from Argentina, and evaluated their influence on bronchodilator desensitization to albuterol over a 4-week treatment. beta2-AR genotypes were determined in 117 children with asthma and 101 of them were under 4 weeks treatment with albuterol. Spirometric changes in FEV(1) were recorded at the beginning (day 1) and at the end of the study (day 30) and compared to genotypes at position 16 and 27 of the receptor. The frequency of the polymorphisms was calculated in all population. The presence of glutamine at position 27 (Gln27) was significantly more frequent in this Argentinean study population than in other Caucasian populations. The homozygosity for Gln27 polymorphism was associated to a desensitization of the receptor with a decline in the bronchodilator response to albuterol after chronic use.
In 2007, Bleeker et al investigated whether beta2-adrenergic receptor (ADRB2) polymorphisms affect response to longacting beta2-agonists in combination with inhaled corticosteroids. Asthmatics were stratified by ADRB2 genotype in two studies to assess the effects of inhaled corticosteroids plus longacting beta2-agonists on asthma exacerbations. In study 1 (double-blind), 2250 asthmatics were randomly assigned to budesonide plus formoterol maintenance and reliever therapy, fixed-dose budesonide plus formoterol, or fixed-dose fluticasone plus salmeterol for 6 months. Study 2 (open-label) consisted of 405 asthmatics and compared an adjustable regimen of budesonide plus formoterol with fixed-dose budesonide plus formoterol and fixed-dose fluticasone plus salmeterol for 7 months. The relation between ADRB2 polymorphism, severe asthma exacerbations, and other asthma outcomes was analysed. Primary endpoints for studies 1 and 2 were severe asthma exacerbation and asthma control as assessed by measures of exacerbations, respectively. In study 1, Gly16Arg genotype had no effect on the percentage of participants with severe exacerbations across all treatment groups (99 [12%] of 833 Gly/Gly, 110 [11%] of 1028 Gly/Arg, and 32 [9%] of 361 Arg/Arg participants). Secondary endpoints, including forced expiratory volume in 1 s, peak expiratory flow, use of as-needed medication, and number of nights with awakenings were similar between genotype groups. No relation was recorded between ADRB2 haplotype and primary and secondary endpoints. In study 2, the frequency of asthma exacerbations (15 [9%] of 168 Gly/Gly, 13 [8%] of 169 Gly/Arg, and 6 [9%] of 67 Arg/Arg participants) and other study endpoints were closely similar for all ADRB2 genotypes.
Hawkins and colleagues (2006) sought to identify ADRbeta2 polymorphisms and haplotype structure in white and African American subjects and to test for genotype and haplotype association with asthma phenotypes. A 5.3-kb region of ADRbeta2 was resequenced in 669 individuals from 429 whites and 240 African Americans. A total of 12 polymorphisms, representing an optimal haplotype tagging set, were genotyped in whites (338 patients and 326 control subjects) and African Americans (222 patients and 299 control subjects). A total of 49 polymorphisms were identified, 21 of which are novel; 31 polymorphisms (frequency > 0.03) were used to identify 24 haplotypes (frequency > 0.01) and assess linkage disequilibrium. Association with ratio (FEV1/FVC)2 for single-nucleotide polymorphism +79 (p < 0.05) was observed in African Americans. Significant haplotype association for (FEV1/FVC)2 was also observed in African Americans. The authors concluded, “these data suggest that the length of a poly-C repeat (+1269) in the 3’ untranslated region of ADRbeta2 may influence lung function, and may be important in delineating variation in beta-agonist responses, especially in African Americans.”
Litonjua (2006) writes the gene that encodes the beta2-adrenergic receptor (ADRB2) is one of the most studied candidate genes in asthma. Candidate gene association studies of ADRB2 and asthma have been dominated by analyses of the two common non-synonymous coding single nucleotide polymorphisms, Arg16Gly and Glu27Gly. Published studies have yielded inconsistent results. Three recent meta-analyses on the effects of these two polymorphisms have found no associations with asthma, although there were suggestions of associations with other asthma-related phenotypes, such as nocturnal asthma and asthma severity. Other recent studies have investigated other single nucleotide polymorphisms in this gene (i.e. single nucleotide polymorphisms in the promoter region and other single nucleotide polymorphisms in the coding region). These analyses have investigated the association between these single nucleotide polymorphisms (and haplotypes of these polymorphisms) and asthma-related phenotypes such as lung function, airways hyperresponsiveness, and response to a bronchodilator, and have suggested that certain regions of the gene may be associated with different phenotypes. Results from these studies, however, have also been inconsistent. Polymorphisms of ADRB2 are not major risk factors for the development of asthma. These polymorphisms are likely to be important, however, in determining drug response. Future studies need to fully characterize all of the variation in the gene and perform comprehensive association studies. Finally, interactions between ADRB2 and other genes in the beta-agonist pathway are an important and active area of research that will shed more light on inter-individual differences in drug response.
In 2005, Taylor et al measured bronchodilator response in patients with asthma stratified by ADRB2 haplotype after eliminating the confounding effect of prior drug treatment with inhaled beta2-agonists and corticosteroids. ADRB2 haplotype was determined in 176 patients with asthma, of whom 161 harbored the six most common combinations. There were no significant differences in bronchodilator response (% improvement in FEV(1)) with respect to any of the major ADRB2 haplotypes or genotypes. The authors concluded, “genetic variation of the ADRB2 does not influence the immediate response to inhaled beta2-agonist. The confounding effect of tolerance resulting from regular beta2-agonist use must be controlled when assessing the pharmacogenetic influences on clinical outcomes with beta2-agonists.”
According to Johnson (2006), the presence of a particular form of the B2-receptor, which might influence clinical efficacy of regular B2-agonists, is of increasing interest in predicting good and poor responders to therapy.
It should have an effect as a cough suppressant but shouldn’t work as a pain medication if my assumption is correct that you’re a CYP2D6 poor metabolizer.
Pharmacogenomic testing will in the future be a very valuable tool but at the moment it’s not advanced enough. From over 200000 drugs in Germany only 40 need a genomic test beforehand to minimize risk. That doesn’t mean the information is not valuable you’re getting now. Metabolism is in my opinion one of the most important aspects of drug use.
But the information is severely lacking. The research isn’t advanced enough to predict too many things. We don’t know which receptor mutations cause what or even which genes affect which disease oftentimes. That will take a long time till we get there.
What I’m saying is, take this test for what it’s worth. It gives you important information on your body but it won’t explain your body to you.
What would be the basis for these assumptions?
I am a hypermetabolizer of antipsychotics. Which would be exacerbated by eating grilled foods or smoking, apparently. I know that they don’t work on my brother, now I know why. SSRI’s would accumulate in my system and quickly achieve a toxic level, so they say. The test encompasses not only CYP’s but also some transport systems like UGT2B15. The ones that are somewhat researched as of right now are in my report, with a comprehensive list of drugs that would specifically be affected by my genomic makeup. I am weird enough that the lab has requested an interview with me for research. Several of my lists are the polar opposite of most of the population, and very unique. I’m sure that will change over time as more people are tested, but right now I’m an outlier genetically.
It doesn’t work as a pain med for me at all, and the results break down several sub-types of CYP2D6. Some of mine are normal, some are not. The test was really mostly to find out that bit, I have a stupid tolerance for things like Adderall, but it seems that those drugs are actually a bad idea for me and my ADD anyway.
cyp2d6 polymorphism, you’re probably a poor cyp2d6 metaboliser, thus you don’t convert enough codeine to morphine. I’m the opposite (ultra-rapid). I need to be careful if taking antitussives and/or painkillers containing codeine.
So you are a CYP1A2 extensive metabolizer which isn’t a polymorphism which means its rare. But beware, that doesn’t hold up for all antipsychotics.
Yes UGTs have great variation too, but only a few are relevant in a few cases.
Why wouldn’t it work as a cough suppressant? Do you have a mutation in your opioid receptors in the cough center of your brain? Note that the active compound for cough suppression IS CODEINE so it doesn’t matter how you metabolize it. For pain it’s the active metabolite morphine which in many people (>1% of the population) doesn’t work for this reason.
I don’t say the test is not worth the money. I’m just underwhelmed by the things I could learn by doing it. If I’d do it, I’d wanna know which receptor has which mutation which causes me to be prone to X.
Still, if you’re a real outlier, the test was good for you. You can make your own conclusions now which steroids to use at which doses (half true, dynamics are missing) which gives you an edge.
Edit: same holds true for SSRIs, they are all different and not metabolized by the same enzymes, so don’t think every SSRI would be a “huge mistake” if you need one, I hope you never will but still.
I don’t know if it does or doesn’t, I never had it for cough, I’ve never had cough as an issue that required medication. Insurance covers the test, so cost isn’t a factor.
That’s actually quite nice. You now know Clopidogrel probably won’t work for you and the serotonin transporter read is very nice. You really are ill equipped for a lot of anti depressants. Reduced metabolism combined with reduced response in some cases. There a still a lot of options left.
The most common reason to get a prescription for codeine is for severe cases of dry cough that’s why it is important in regard to the compound.
I had a bottle of liquid codeine after my tonsillectomy when I was 16. I started at the bottle dose, did zero. I took more. Zero. I finally turned the bottle up and chugged it. All I got was relief for a minute or so because it coated my throat. I had assumed that Tylenol with codeine didn’t work because I didn’t take enough of them, but now I have a reason.
Haha nice story, we often learn through trial and error
Guess you had to eat more ice cream then
Fudgesicles are king for this. Just sayin…