Say you slip with the knife while cutting up an apple for lunch. Ouch! It may bleed a bit, but you know that pretty soon, it will stop. The physiological trick here is to ensure the clotting isn’t too quick. If clotting occurs faster or thicker than it should, the risk of clots in our vessels increases.
The ITGB3 Gene – PIA1/A2 mutation
A whole cascade of events takes place to form a blood clot. The ITGB3 gene encodes integrin Subunit Beta 3, which is a part of how platelets form clots.
Fibrinogen is the protein activated to create the fibers that shore up the clot.
The clotting action is vitally important when you cut yourself — but clotting too much or too quickly can also be a problem. Blood clots can cause heart attacks and strokes. Additionally, blood clots that form in the large veins of the leg or arm can cause deep vein thrombosis.
Does the PIA1/A2 variant increase cardiovascular event risk?
Hundreds of studies have been done on the ITGB3 genetic variant known as PIA1/A2. Here is an overview of some of the findings:
- A study of 80 men aged 20-25 found that those carrying the A2 variant had faster blood clotting times. The study also found that many (but not all) of the variant carriers were resistant to aspirin’s blood-thinning effects.[ref]
- Women carrying the variant were at an increased risk of having recurrent miscarriages.[ref]
- A study of men who died of sudden cardiac death found that the A2 variant more than doubled the risk of sudden cardiac death under the age of 50.[ref]
- The results of one study that included both men and women found only women who carried the A2 variant were at a higher risk of deep venous thrombosis.[ref]
- An overall meta-analysis combining the data from 14 studies concluded a statistical increase in the risk of heart attacks exists. This wasn’t a big increase in risk for the overall population (8%), but it had a slightly bigger impact on people younger than age 45 (a 20% increase in risk). Keep in mind, though, that the risk of heart attack is low in people younger than 45.[ref]
- Researchers looked at 1,202 Caucasian patients in an atherosclerosis study and found the A2 variant carriers may be predisposed to an “increased risk of atherosclerotic plaque rupture.”[ref]
- A study of Pakistani patients found the variant has no impact on aspirin resistance.[ref]
- A study of male physicians found carrying the A2 variant did not increase the risk of stroke, heart attack, or DVT.[ref]
While this genetic variant seems to increase the overall risk for various cardiovascular events, it is probably acting together with lifestyle factors and other genetic variants.
Protection from the hantavirus:
Most genetic variants that have a downside also have a positive one. There is a reason the variant survives in the population. Tradeoffs.
The downside of the A2 variant is obvious – increased early heart attack deaths, especially without modern medical care.
If all people carrying this ITGB3 gene variant died from early heart attacks, at some point, the variant should have dwindled out in the human population. But, balancing the negative is a positive reason the variant still is found in the population. Research shows the variant offers protection from dying from pathogens that cause excessive bleeding.
For example, carriers of the A2 variant are protected from getting the hantavirus. The spreading of hantavirus occurs from mouse and rat feces, and in Chile, it has a mortality rate of 30-35%.
The hantavirus causes cardiopulmonary responses due to increased vascular permeability. The study found that those people carrying the A2 variant were less likely to get the hantavirus. The study looked at who got the virus and at people exposed to the virus who didn’t get it. None of the hantavirus patients carried two copies of the PIA2 variant. In the group exposed to the virus but who didn’t get sick, 11% of them carried two copies of the variant.[ref]
While you may be thinking that the hantavirus is a new, recently discovered pathogen, historical records show that the English Sweating sickness had similar patterns and symptoms. The English Sweat is first recorded in the time of Henry VIII, with recurrences periodically over the next century or two. The timeline, conditions, death rate, and symptoms fit with hantavirus spread by rodents. Additionally, outbreaks of similar symptoms periodically spread across Europe and Russia in years with similar weather patterns.[ref]
PIA1/A2 Genotype Report:
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Check your genetic data for rs5918 (23andMe v4, v5; AncestryDNA):
- C/C: two copies of the A2 variant, increased risk of heart disease, may not benefit from aspirin for heart attack prevention, protection against Hantavirus[ref][ref][ref][ref]
- C/T: somewhat increased risk of heart disease, may not benefit as much from aspirin for heart attack prevention, protection against Hantavirus[ref][ref][ref]
- T/T: typical
Members: Your genotype for rs5918 is —.
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