Transmembrane Protease, Serine 6 (TMPRSS6) gene is associated with the synthesis of transmembrane protease, serine 6 (also known as matriptase-2), a liver serine protease. TMPRSS6 cleaves the bone morphogenetic protein (BMP) and down-regulates the iron hormone hepcidin, facilitating iron absorption. Inactivation of TMPRSS6 is associated with iron deficiency anemia.
There are two single nucleotide polymorphisms associated with this gene, rs855791 and rs4820268. Variations in this gene are shown to be associated with serum iron, hemoglobin transferrin saturation and erythrocyte traits.
Iron is essential for production of blood and most of the body's iron (70%) is found in the red blood cells of the blood called hemoglobin and in muscle cells called myoglobin. Hemoglobin transfers oxygen in the blood from the lungs to the tissues. Myoglobin, present in muscle cells, transports, stores and releases oxygen.
Iron is also a constituent of certain proteins (6%) and is essential for energy metabolism and for respiration. It is a component of enzymes that are involved in the synthesis of collagen as well as for certain neurotransmitters. Iron is also required for optimum immune function.
Nearly 25% of the iron is stored as ferritin in the body.
- On an average 1,000 mg of iron is stored among adult men.
- 300mg of iron is stored among women
Does your 23andme, Ancestry DNA, FTDNA raw data have TMPRSS6 gene variant information?
| CHIP Version | TMPRSS6 SNPs |
| 23andMe (Use your 23andme raw data to know your TMPRSS6 Variant) | |
| v1 23andme | Present |
| v2 23andme | Present |
| v3 23andme | Present |
| v4 23andme | Present |
| V5 23andme (current chip) | Present |
| AncestryDNA (Use your ancestry DNA raw data to know your TMPRSS6 Variant) | |
| v1 ancestry DNA | Present |
| V2 ancestry DNA (current chip) | Present |
| Family Tree DNA (Use your FTDNA raw data to know your TMPRSS6 Variant) | |
| OmniExpress microarray chip | Present |
Association with Iron Levels:
In a study conducted on 2100 elderly women, people with the T variant of the gene (rs855791) were associated with lower levels of serum iron and hemoglobin. In another study conducted on 14,100 Danish men, men with the T variant were shown to be associated with lower levels of iron.
In another study conducted on about 600 people, the G variant of the gene (rs4820268) is associated with lower hepcidin levels than the A variant.
| Genotype rs855791 | Phenotype | Recommendation |
| TT | [Limitation] More likely to have lower serum iron and hemoglobin levels | Likely decrease in iron levels Include chicken liver, pumpkin seeds, spinach, tofu, almonds and baked beans. Since there is a genetic predisposition for lower levels of iron, it is recommended to consume more than the daily recommended amount of iron |
| CT | Moderate level of serum iron | No genetic predisposition for lower iron levels so daily recommended level of iron may be consumed. Men should consume 8mg/day, women between 19-50 years should consume 18 mg/day and women over 50 years should consume 5mg/day |
| CC | [Advantage] More likely to have higher serum iron and hemoglobin levels | No genetic predisposition for lower iron levels so daily recommended level of iron may be consumed. Men should consume 8mg/day, women between 19-50 years should consume 18 mg/day and women over 50 years should consume 5mg/day |
| Genotype rs4820268 | Phenotype | Recommendation |
| GG | [Limitation] More likely to have lower hemoglobin levels | Likely decrease in iron levels Include chicken liver, pumpkin seeds, spinach, tofu, almonds and baked beans. Since there is a genetic predisposition for lower levels of iron, it is recommended to consume more than the daily recommended amount of iron |
| AG | Moderate level of hemoglobin | No genetic predisposition for lower iron levels so daily recommended level of iron may be consumed. Men should consume 8mg/day, women between 19-50 years should consume 18 mg/day and women over 50 years should consume 5mg/day |
| AA | [Advantage] More likely to have higher hemoglobin levels | No genetic predisposition for lower iron levels so daily recommended level of iron may be consumed. Men should consume 8mg/day, women between 19-50 years should consume 18 mg/day and women over 50 years should consume 5mg/day |
References:
- https://www.ncbi.nlm.nih.gov/pubmed/26597663
- https://www.ucsfhealth.org/education/hemoglobin_and_functions_of_iron/
- https://www.ncbi.nlm.nih.gov/pubmed/22885719
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3135421/
- https://www.ncbi.nlm.nih.gov/pubmed/22301935?dopt=Abstract
“Nutrigenetics, fitness genetics, health genetics are all nascent but rapidly growing areas within human genetics. The information provided herein is based on preliminary scientific studies and it is to be read and understood in that context.”
