Do you end up getting sore after pretty much every work out at the gym? A deficiency caused by the AMPD1 genetic variant could be the cause. (Or you could be over-doing it :-)
AMPD1(Adenosine monophosphate deaminase)
Adenosine monophosphate deaminase is an enzyme coded for by the gene AMPD1, which acts in the skeletal muscles to convert AMP to IMP.
In a nutshell, this is an enzyme that your muscles use when they need to make a lot of ATP for energy.
There is one common AMPD1 genetic variant, known as C34T, causing a decrease in the function of this enzyme for people with one copy of the variant. People with two copies of this variant have a non-functioning enzyme. Caucasian and African populations carry one copy of the variant at a frequency of about 10%. It is much less frequent in other population groups.
AMPD1 deficiency, also known as myoadenylate deaminase deficiency, has varying effects on exercise performance, heart attack response, and methotrexate (cancer drug) response. It causes sore muscles and possibly muscle spasms when working out. But it also may be protective against heart disease.[ref]
Does AMPD1 deficiency mean that you can’t work out? Absolutely not. It just means that you may have more pain or muscle soreness than other people do. It’s just genetic – and doesn’t mean that you are a workout wuss :-)
AMPD1 Genetic Variant:
Check your genetic data for rs17602729 (23andMe v4, v5; AncestryDNA):
Members: Your genotype for rs17602729 is —.
- A recent study found that those with an A allele “require longer rest periods between bouts of weight training, require longer between sessions and have increased perceived pain post-training”.[ref]
- In a study of elite triathlon athletes, AMPD1 was found to be the only significant genetic factor for performance time.[ref]
- A study of Lithuanian athletes found no athletes with the AA genotype and the AG genotype likely affected anaerobic performance more than aerobic performance.[ref]
- A study of elite rowers also found that the A allele was found much less often in the group.[ref]
- One report sums up the exercise impact this way: “The frequency of the mutant allele is 8–11% in sedentary Caucasians, with only 2% of the population being homozygous for this mutation (20% are heterozygous) . AMPD muscle activity is greatly diminished even in heterozygous individuals, reaching only ~39% activity of healthy controls . Furthermore, in some heterozygotes, AMPD activity has been reported to be as low as 16% of its normal activity . As a result, deleterious effects on exercise capacity associated with the C34T mutation have been reported, even in heterozygotes.”[ref]
Infection / Endotoxin studies:
- A study of healthy males given endotoxin (e. Coli) found that those with the AMPD1 polymorphism had higher adenosine levels, but the higher levels did not protect against subclinical organ damage.[ref]
- While not associated with susceptibility to infection, a study of pneumonia patients found that the AMPD1 polymorphism “is associated with more pronounced immunoparalysis in patients with sepsis, and shows a tendency towards increased mortality”.[ref]
Rheumatoid arthritis /methotrexate studies:
- A study found that AMPD1 deficiency is associated with the response to methotrexate in rheumatoid arthritis.[ref]
- The AMPD1 polymorphism is associated with a good response to methotrexate.[ref]
- According to a 2015 study in a Malaysian population, AMPD1 polymorphisms may play a significant role in hypertension.[ref]
- A meta-study looks at the generally beneficial role of the AMPD1 polymorphism in heart disease.[ref]
- Another study found that being heterozygous for the AMPD1 variant led to better prognosis in cardiovascular disease [ref]
Ribose has been suggested in several studies and in online forums for AMPD1 deficiency. It can be purchased online and at health food stores. It is a white powder and is a type of simple sugar. Some people with blood sugar regulation problems report having problems with hypoglycemia when taking it.[ref]
Related Genes and Articles:
PPAR-Delta: Burning off the fat
PPARδ is a key player in how and when your muscles burn fat for fuel. Genetic variants in the PPARD gene impact how well your muscles utilize fatty acids. These variants also impact how much of a fat-burning benefit you get from exercise.
If you are at the top of your sport and looking to optimize, genetics does come into play with muscle composition and endurance.
(originally published May 2017, revised and updated Sept. 2019)