|(A;A)||3||AMPD1 deficiency homozygous (orientation reversed)|
|(A;G)||2.8||AMPD1 deficiency heterozygous (orientation reversed)|
|(C;T)||2.8||AMPD1 deficiency heterozygous|
|(G;G)||0||normal (orientation reversed)|
|(T;T)||3||AMPD1 deficiency homozygous|
rs17602729, a SNP located in the AMPD1 gene and also known as 'C34T', has at times been called the "most prevalent genetic disease mutation", at least in Caucasians. [PMID 11331279] Perhaps up to 10% of Caucasians and African-American carry one C34T allele (i.e. carry one rs17602729(A) allele) - and actually, most of them are unaware of any medically related issues since they don't typically have any particular symptoms that would warrant a trip to the doctor.
So what's the issue? The AMPD1 gene encodes the enzyme adenosine monophosphate deaminase, which is one of the key enzymes used to process the energy source ATP. The C34T variation causes a premature stop in the protein, leading to a nonfunctional AMPD1 enzyme. Some individuals - but by no means all or even a majority apparently - who are AMPD1 deficient get muscle cramps and pains when they exert themselves. The most common genotype bringing this about is rs17602729(A;A), i.e. the individuals who carry two copies of the C34T allele and therefore have no functioning AMPD1 allele. It is not known why only some of C34T homozygotes experience muscle myalgia.
Heterozygotes, i.e. rs17602729(A;G) individuals, do not seem to suffer any exercise or fitness related deficit. In fact, one of the best elite Caucasian distance runners is known to be a C34T heterozygote. [PMID 16505069]
In fact, heterozygotes for rs17602729 may even have advantages over those lacking a C34T allele. The most striking study reported that C34T heterozygotes are 8.6 fold (CI: 3.05 - 23.87) more likely to survive for more than 5 years without needing a heart transplant after a congestive heart failure related hospitalization than the wild-type homozygotes (i.e. rs17602729(G;G) homozygotes). [PMID 10086964] Similarly, C34T heterozygotes with coronary artery disease seem to fare better than wild-type homozygotes. [PMID 11028479]
This is one of the SNPs reported by NutraHacker.[PMID 21211004] Circulating adenosine increases during human experimental endotoxemia but blockade of its receptor does not influence the immune response and subsequent organ injury
|Disease||Muscle AMP deaminase deficiency|
|CLNDBN||Muscle AMP deaminase deficiency|
|CLNSRC||GTR OMIM Allelic Variant|
[PMID 18852891] Distribution and effects of nonsense polymorphisms in human genes.
[PMID 18974781] Cataloging coding sequence variations in human genome databases.
[PMID 19237423] Is there an optimum endurance polygenic profile?
|qualified_impact||Low clinical importance, Likely pathogenic|
|summary||Causes Adenosine Deaminase Deficiency in a recessive manner. Most of the time individuals do not report symptoms, but when symptoms do exist they to be post-exercise symptoms of muscle weakness, muscle pain, and getting tired more quickly.|
[PMID 23681449] Genes for Elite Power and Sprint Performance: ACTN3 Leads the Way
[PMID 25682119] Genetic Factors Associated with Exercise Performance in Atmospheric Hypoxia