Is Rheumatoid Arthritis Genetic—And Does Family History Boost Your Risk?
A large number of health conditions list "genetics" or "family history" as risk factors—everything from obesity and asthma to cancer and diabetes make it clear that if the condition runs in your family, you are at a higher risk for developing it yourself.
The same can be said for rheumatoid arthritis (RA), an autoimmune disease that causes your immune system to attack the healthy tissue of your joints. But while RA does include genetics as a risk factor, genetics aren't the only thing that can trigger the disease and, in some cases, genetics have very little to do with whether or not a person develops RA.
"There are there some genes transmitted from one family member to another that might predispose you to RA," says Jonathan Greer, MD, rheumatologist with Arthritis & Rheumatology Associates of Palm Beach and medical advisor to CreakyJoints. "But having the genes only makes it more likely [you'll develop RA], not guaranteed."
So is RA genetic or not? What about hereditary? And what are your chances of developing RA if someone else in your family has it? Here's what you need to know about the genetic component of RA, from what that actually means to how it affects your overall risk.
First Off: Do Genetic and Hereditary Mean the Same Thing?
The words "genetic" and "hereditary" are usually used interchangeably to describe health conditions passed on from one family member to the next (like a parent to their child). But technically, there is a difference between the terms.
- A genetic condition is one that occurs because of a gene mutation. Sometimes these mutations are passed on through family DNA, but other times, they happen totally randomly or because of an external or environmental factor.
- A hereditary condition, on the other hand, is always handed down from parent to child through genetic makeup. Hereditary conditions don't occur "naturally," i.e., as the result of external or environmental factors.
In other words: a hereditary condition is always genetic, but not all genetic conditions are hereditary.
Is Rheumatoid Arthritis Genetic or Hereditary?
OK, so here's where things get a little tricky: the answer is both...and also neither!
RA can be caused by an inherited gene or a random gene mutation, so to say RA is strictly hereditary isn't accurate. While the genes that cause RA can be passed down through family, many cases of RA happen independently of any family history. Likewise, most people with RA have some genetic markers for the disease, but that doesn't mean everyone with the genes will ultimately end up with RA.
According to Robert Koval, MD, an Austin-based rheumatologist at Texas Orthopedics, the risk of RA in the general population is between 1% and 2%; with a family history, your risk may double or even triple, but that still only leaves you with less than a 10% chance at most.
"The odds are in your favor, but you should be aware of symptoms if you have a family history," Dr. Koval tells Health.
He notes that the incidence of RA in identical twins, who share 50% of their genes, is higher than it is in non-identical twins, but still quite low: if one identical twin has RA, there's still less than a 15% chance the other twin will have it as well.
Overall, about 60% of RA cases can be traced back to inheritability versus other factors, according to the UK's National Rheumatoid Arthritis Society. Still, that doesn't mean you, personally, have a 60% chance of developing RA with a family history; the individual risk is much, much lower.
What Genes Can Cause RA?
There are over 100 possible genes that could trigger the heightened immune response that causes RA, some of which may be inherited while others may occur naturally, as the result of random gene mutations.
However, researchers have identified four genetic markers they know to be linked to RA:
- HLA-DR4, the most prominent risk factor for RA, which makes you five times more likely to develop RA than someone without it.
- STAT4, a gene responsible for immune system regulation.
- TRAF1 and C5, genes known to cause chronic inflammation.
- PTPN22, which may trigger RA and affect its progression.
Dr. Greer says that because there is such a large number of genes that can cause RA, just having one gene doesn't mean you'll develop the disease; there are lots of changes that can take place in the body, from your gut to your mouth, that can trigger the onset of RA if you are already predisposed genetically.
If RA Isn't Always Genetic, Then What Causes It?
People who develop RA do seem to have some genes in common, indicating that genetics predisposes you to developing the disease. But since the individual chances of having RA with and without family history are still fairly low, what else causes RA to develop?
The answer is external factors, which play a huge part in turning the genetic possibility of RA into a reality. They include the following:
RA is far more common in women than it is in men, so simply being female (with the right combination of genes) can increase your chances of developing RA. Per Brigham and Women's Hospital in Boston, about 75% of RA patients are female.
RA can develop at any age, says Dr. Koval, though there are still observable patterns. "For females, in your 50s—around the time of menopause—is common, and so is your 20s [because of hormonal changes]," he explains. "Childbirth, and the major hormone shift it causes in the first six months, is a common time for RA to present." Beyond that, Dr. Greer notes that the reduced efficiency of our immune system as we age leaves people in their 70s and 80s especially vulnerable to developing RA as well.
This is a broad category, including everything from diet to illness to toxin exposure. The single biggest lifestyle risk factor, however, is smoking, especially if you are a heavy smoker or have smoked for more than 20 years, according to the Mayo Clinic. (Smoking can also increase your RA symptoms, BTW, as the Arthritis Foundation points out.)
The Bottom Line
Genes are undeniably a key piece of the RA puzzle; we know a large number of genes are associated with RA, and any one of them can increase your general risk for the disease. In some cases, those genes may be inherited, and in others, they might occur randomly. But genes remain only a piece of the puzzle, not the whole puzzle.
"It's a complicated issue," says Dr. Greer. "If you have a predisposed patient who comes into contact with an environmental stimulus, it can trigger the disease."
As for whether or not RA is hereditary, within families, a history of RA slightly increases your risk of developing the disease but is by no means a guarantee. Much of the time, something else—like age, gender, or certain lifestyle factors—combines with your genetic makeup to create the hyperinflammatory response that leads to RA (family history or not).
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