Markers / Condition
Which genes affect pain sensitivity and inflammation?
Pain is a signal, not a sensation, and how loudly it is sent varies between people for reasons that are partly genetic. Three of the variants here came from Neanderthals. Inflammation sits beside it because the same machinery that defends you acutely damages you chronically.
The markers
| Marker | Gene | What it does | Evidence |
|---|---|---|---|
| rs3750904 | SCN9A | Neanderthal: pain sensitivity, D1908G | strong |
| rs4369876 | SCN9A | Neanderthal: pain sensitivity, V991L | strong |
| rs12478318 | SCN9A | Neanderthal: pain sensitivity, M932L | strong |
| rs1205 | CRP | Your baseline C-reactive protein | established |
| rs2228145 | IL6R | The interleukin-6 receptor, and a drug target found by genetics | established |
| rs1800629 | TNF | Tumour necrosis factor, the inflammation dial | moderate |
| rs1143634 | IL1B | Interleukin-1 beta, the fever signal | moderate |
| rs1799971 | OPRM1 | Opioid receptor variant A118G | moderate |
Neanderthal: pain sensitivity, D1908G
rs3750904 · SCN9A
Neanderthals carried three changes in the sodium channel that carries pain signals. People who inherited them report more pain, and in laboratory testing have a lower threshold for mechanical pain. The variants are essentially absent in Europeans and common in Latin American populations.
Two copies: Inherited from both parents
Neanderthal: pain sensitivity, V991L
rs4369876 · SCN9A
The second of the three Neanderthal changes in the pain-signalling sodium channel.
Two copies: Inherited from both parents
Neanderthal: pain sensitivity, M932L
rs12478318 · SCN9A
The third of the three Neanderthal changes in the pain-signalling sodium channel.
Two copies: Inherited from both parents
Your baseline C-reactive protein
rs1205 · CRP
CRP is the inflammation marker most often measured in a blood test. Part of your baseline is genetic rather than a reflection of how inflamed you are, which matters when a doctor reads the number.
Two copies: You have the lower-CRP version on both copies
The interleukin-6 receptor, and a drug target found by genetics
rs2228145 · IL6R
IL-6 is a central inflammation signal. This variant shifts receptors off cell surfaces into the blood, which dampens the signal, and carriers have a slightly lower risk of coronary heart disease. That finding is a large part of why IL-6 blockade was pursued as a heart drug at all.
Two copies: You carry two copies
Tumour necrosis factor, the inflammation dial
rs1800629 · TNF
TNF is one of the body's strongest inflammatory signals, and blocking it is the basis of several major drugs for rheumatoid arthritis and inflammatory bowel disease. This promoter variant is associated with producing more of it.
Two copies: You carry two higher-output copies
Interleukin-1 beta, the fever signal
rs1143634 · IL1B
IL-1 beta is the molecule that raises your body temperature during infection. Fever is a defence, not a symptom, and this variant is associated with producing more of the signal that triggers it.
Two copies: You carry two higher-output copies
Opioid receptor variant A118G
rs1799971 · OPRM1
This changes the main receptor that opioid painkillers act on. It has been studied for morphine dose requirements after surgery and for response to naltrexone in treating alcohol dependence.
Two copies: Two copies of the variant receptor
Which versions do you carry?
All of these are readable from an ordinary home DNA test file, in your browser, without uploading it anywhere.
Read my fileCommon questions
Which genes affect pain sensitivity and inflammation?
Pain is a signal, not a sensation, and how loudly it is sent varies between people for reasons that are partly genetic. Three of the variants here came from Neanderthals. Inflammation sits beside it because the same machinery that defends you acutely damages you chronically. The markers most often cited are rs3750904 in SCN9A, rs4369876 in SCN9A, rs12478318 in SCN9A, rs1205 in CRP, rs2228145 in IL6R.
What does rs3750904 do?
Neanderthals carried three changes in the sodium channel that carries pain signals. People who inherited them report more pain, and in laboratory testing have a lower threshold for mechanical pain. The variants are essentially absent in Europeans and common in Latin American populations. Carrying two copies: inherited from both parents.
What does rs4369876 do?
The second of the three Neanderthal changes in the pain-signalling sodium channel. Carrying two copies: inherited from both parents.
What does rs12478318 do?
The third of the three Neanderthal changes in the pain-signalling sodium channel. Carrying two copies: inherited from both parents.
What does rs1205 do?
CRP is the inflammation marker most often measured in a blood test. Part of your baseline is genetic rather than a reflection of how inflamed you are, which matters when a doctor reads the number. Carrying two copies: you have the lower-crp version on both copies.
Reference information, not medical advice and not a diagnosis. See the medical disclaimer.