SNPwatch: Genetic Variation May Help Immune System Put Up Just The Right Amount Of Fight

SNPwatch gives you the latest news about research linking various traits and conditions to individual genetic variations. These studies are exciting because they offer a glimpse into how genetics may affect our bodies and health; but in most cases, more work is needed before this research can provide information of value to individuals. For that reason it is important to remember that like all information we provide, the studies we describe in SNPwatch are for research and educational purposes only. SNPwatch is not intended to be a substitute for professional medical advice; you should always seek the advice of your physician or other appropriate healthcare professional with any questions you may have regarding diagnosis, cure, treatment or prevention of any disease or other medical condition.


When it comes to fighting infections, it might seem like the more immune system firepower, the better. But in reality, the body’s response to bacteria and other invaders is a delicate balancing act. If the response is too little or too late, an infection can become unbeatable. But if the immune system comes on too strong, it may end up doing more harm than good.

New research suggests a genetic variation that arose in the first inhabitants of Europe may have helped them and their descendants hit the immune response sweet spot. These results, published online this week in Proceedings of the National Academy of Sciences, may also help scientists better understand sepsis, a state of whole-body inflammation in response to infection that is the tenth leading cause of death in the United States, with an annual cost of nearly $17 billion.

Studies have shown that people who have one copy of a T at rs8177374 in the TIRAP gene are less susceptible to infection with malaria, tuberculosis, bacteremia and pneumococcal disease. Scientists know that the TIRAP gene encodes a protein involved in helping the body recognize and destroy a broad range of pathogenic bacteria. But what they haven’t known until now is how rs8177374 might affect this process.

To investigate, Bart Ferwerda of the Nijmegen Institute for Infectious Inflammation and Immunity in the Netherlands and an international team of collaborators infused volunteers with LPS, a toxin found in the outer membranes of some bacteria.  They found that for each T at rs8177374, a person’s body released more pro-inflammatory signaling molecules into the bloodstream in response.

(23andMe customers can check their data for rs8177374 using the Browse Raw Data feature.)

The T version of rs8177374 occurs at much higher frequencies in people with European ancestry than either Africans or Asians.  According to the authors, this suggests that the mutation didn’t arise until after the ancestors of East Asians and Europeans had split apart – sometime after the out-of-Africa migration but before the first people moved into Europe about 40,000 years ago.

Traditional thinking is that a person who ends up with high levels of pro-inflammatory signaling molecules in response to an infection is in trouble, because over-inflammation can lead to shock and death. But the authors suggest this may be true only in people who are already suffering from sepsis.  In the initial stages of infection, high levels of pro-inflammatory molecules could actually be very beneficial.

Their theory is that in the harsh environment the ancestors of modern Europeans encountered, those with one copy of T at rs8177374 were more resistant to infections.  But if an infection did set in, their immune responses weren’t so overzealous that they were at risk for septic shock.  People with a T at each copy of rs8177374, however, would have been at a disadvantage. The chance of going shock in response to an infection would have outweighed the benefit of being less infectable to begin with. This, the authors suggest, is why the T version of rs8177374 didn’t take over completely in the population.

  • nick

    I wonder if Ts might occur more frequently than expected at this location in autoimmune diseases.

  • askalice

    I have this exact snp and have often wondered why I have never had strep throat even having been exposed to it countless times by my own children. I don’t “catch” what everyone else around me gets but I am now in my 50’s and am becoming taken over with arthritic pain.

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