AMPD1 Deficiency — Varying effects of the polymorphism

AMPD1 DeficiencyAdenosine Monophosphate deaminase is an enzyme coded for by the gene AMPD1 and acts in the skeletal muscles to convert AMP to IMP.  There is one common polymorphism, C34T, that causes a decrease in function of this enzyme.  It is heterozygous in 10% – 15% in Caucasians and Africans, while  ~ 1% are homozygous for the variant.  AMPD1 deficiency, also known as myoadenylate deaminase deficiency, has varying effects on exercise performance, heart attack response, and methotrexate response.

The Genetics Home Reference give an introduction to this gene and its function:

“The AMPD1 gene provides instructions for producing an enzyme called adenosine monophosphate (AMP) deaminase. This enzyme is found in the muscles used for movement (skeletal muscles), where it plays a role in producing energy. Specifically, during physical activity, this enzyme converts a molecule called adenosine monophosphate (AMP) to a molecule called inosine monophosphate (IMP) as part of a process called the purine nucleotide cycle. This cycle reuses molecules called purines, which are a group of building blocks of DNA (nucleotides), its chemical cousin RNA, and molecules such as AMP that serve as energy sources in the cell. As part of the purine nucleotide cycle, AMP deaminase converts AMP to IMP, and as the cycle continues, molecules are produced that the muscle cells can use for energy. Skeletal muscle cells need energy to function and move the body. “

A recent study gives a more in-depth explanation:

“AMPD catalyzes the intracellular conversion of AMP into IMP (inosine monophosphate). Subjects heterozygous for this variant allele appear to have a 50% reduction in enzyme activity [33]. Interestingly, heterozygosity was recently associated with an improved cardiovascular prognosis in patients with coronary artery disease, probably because of an increased conversion of AMP into adenosine with subsequent increased adenosine concentrations and subsequent organ protection during ischemia.”

AMPD1 Genetic Polymorphism:

rs17602729 is also known as C34T in studies.  Most studies refer to the minor allele (less common variant) as T, but in 23andMe data it will be A.

Check your 23andMe results for rs17602729:

  • AA: loss of function variation for AMP Deaminase (increased adenosine formation, muscle soreness in exercise, various other effects)
  • AG: reduced AMP Deaminase function
  • GG: normal type

Exercise studies:

  • 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”
  • In a study of elite triathlon athletes, AMPD1 was found to be the only significant genetic factor for performance time.
  • A study of Lithuanian athletes found no athletes with the AA genotype and that the AG genotype likely affected anaerobic performance more than aerobic performance.
  • A study of elite rowers also found that the A allele was found much less often in the group.
  • 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) [14]. AMPD muscle activity is greatly diminished even in heterozygous individuals, reaching only ~39% activity of healthy controls [11]. Furthermore, in some heterozygotes, AMPD activity has been reported to be as low as 16% of its normal activity [15]. As a result, deleterious effects on exercise capacity associated with the C34T mutation have been reported, even in heterozygotes.”

Infection / Endotoxin studies:

  • 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.
  • 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”.

Rheumatoid arthritis /methotrexate studies:

  • A study found that AMPD1 deficiency is associated with the response to methotrexate in rheumatoid arthritis. [study]
  • The AMPD1 polymorphism is associated with a good response to methotrexate according to this study.

Heart Disease:

Diet interaction:

  • A mouse study found that AMPD1 deficiency along with a high-fat diet (compared to normal chow diet) upregulated mTOR, which is involved in insulin resistance, among other things.  A previous study had also found that “Disruption of the AMPD1 gene leads to a less severe state of insulin resistance, improved glucose tolerance and enhanced insulin clearance in mice fed a high fat diet.”
  • Alternatively, another study that was previously done in mice did not find that AMPD1 inhibitor drugs helped with insulin resistance.  Note that mouse studies may not exactly correlate to human studies in the way AMPD1 works.

Diet and Supplements for AMPD1 deficiency:

  • Ribose has been suggested in several studies and in online forums for AMPD1 deficiency.  It can be purchased through Amazon and at health food stores. It is a white powder and is a sugar.  Some people with blood sugar regulation problems report having problems with hypoglycemia when taking it.
  • Creatine supplements have also been used for AMPD1 deficiency.  Studies have shown varying results for the impact of creatine.  [study] [study]

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