Is Rheumatoid Arthritis Hereditary?

Rheumatoid arthritis is a chronic inflammatory disorder that affects several joints of the body, including the hands and feet.1 Rheumatoid arthritis is an autoimmune disorder that makes the body’s immune system to mistakenly start attacking the membranes lining the joints. This leads to inflammation and pain along with damage to other organs, including the eyes, heart, lungs, and blood vessels.

Rheumatoid arthritis is a chronic disease, meaning it gets worse with time. People with this condition experience periods of flare-ups during which their symptoms are aggravated, followed by periods of remission during which the symptoms lessen in intensity or may even go away completely.2

According to the American College of Rheumatology, nearly 1.3 million in the United States alone have rheumatoid arthritis.3 Globally, the annual incidence of rheumatoid arthritis is estimated to be around three cases per 10,000 population, while the prevalence rate is approximately one percent.4

The exact cause of rheumatoid arthritis remains unclear, and as is the case with most autoimmune diseases, researchers believe that specific genes are responsible for increasing the risk of some people developing rheumatoid arthritis. However, most experts do not consider rheumatoid arthritis to be an inherited disease. This means that it is not possible for a geneticist to calculate your individual chances of getting rheumatoid arthritis based on your family history.

There are several other factors also that are known to trigger an abnormal autoimmune response in the body that causes it to mistakenly attack itself. These include:

Is Rheumatoid Arthritis Hereditary?

Is Rheumatoid Arthritis Hereditary?

While doctors and researchers do not entirely understand the exact cause of rheumatoid arthritis, they do believe that having a family history of the disease can increase a person’s risk of developing rheumatoid arthritis. However, no one has been able to correctly predict whether a person with genetic risk factors for rheumatoid arthritis will go on to develop the disease or not.

It is known that rheumatoid arthritis is usually caused by a combination of environmental and genetic factors. For example, a study discovered that children who grew up with mothers who were chronic smokers had twice the risk of developing rheumatoid arthritis once they became adults.5

According to the US Centers for Disease Control and Prevention, the risk for developing rheumatoid arthritis is believed to be the highest when a person has certain genes that are associated with this disease and, at the same time, also have other risk factors like obesity or smoking, which increases the overall risk of developing the disease manifolds.6

Many researchers also say that the reason no one has been able to predict correctly if rheumatoid arthritis is an inherited disease is that there is a lack of large-scale population studies that are actually required to fully understand what genetics are at play behind this disease. Such large-scale studies are also not economically feasible, which is perhaps why they have not been carried out.7

Does Genetics Play a Role in Rheumatoid Arthritis?

The immune system is responsible for protecting you from attacks by foreign invaders, including bacteria and viruses. However, sometimes the immune system gets tricked into mistakenly attacking the healthy parts of the bodies.

Researchers have been able to identify several of the genes that control these immune responses and having these genes dramatically increases a person’s risk for rheumatoid arthritis. However, not everyone who has rheumatoid arthritis has these genes, and not everyone with these genes goes on to have rheumatoid arthritis.8

Till today, researchers have isolated and identified over 100 locations in the human DNA that are believed to be associated with rheumatoid arthritis.7 One such example is the human leukocyte antigen (HLA) gene.9 Doctors have discovered that the HLA-DrB1 gene is associated with rheumatoid arthritis. The HLA gene is responsible for distinguishing between the proteins of the infecting microbe and your body’s proteins. This gene is considered to be one of the biggest known genetic risk factors for rheumatoid arthritis.

According to data from the Arthritis Foundation, it has been found that people who have the HLA-DRB1 genetic marker are almost five times more likely to develop rheumatoid arthritis as compared to people who do not.10

Some of the other genes that are believed to be associated with rheumatoid arthritis are as follows:

  • STAT4: This gene is responsible for controlling the manner in which the body regulates and activates the immune system and immune response.11
  • PTPN22: This gene is believed to play a role in how the disease develops and progresses. This gene is also known to be linked with the onset of rheumatoid arthritis.12
  • TRAF1 and C5: These genes are associated with chronic inflammation.13

Some of the genes that are linked with rheumatoid arthritis are also known to be involved in causing other autoimmune diseases such as multiple sclerosis and type 1 diabetes. This is why many times, a person ends up developing more than one autoimmune disease.

However, while these genes have been identified as being associated with rheumatoid arthritis, doctors still do not understand the exact process as to how a person gets these genes. It is possible that one parent passes down a mutated gene, or some external factor modifies the existing genes. At the same time, though, not everyone who has one of these rheumatoid arthritis-linked genes, go on to develop the condition.

What If A Family Member Has Rheumatoid Arthritis?

A study found that the first-degree relatives of a person who has rheumatoid arthritis are nearly three times more likely to develop the disease as compared to the first degree relatives of people without rheumatoid arthritis.14 This means that children, parents, and siblings of a person with rheumatoid arthritis are at a slightly higher risk of developing the illness. However, this risk does not take into account any environmental factors.

Another study reported that genetic factors account for almost 52 to 67 percent of all the causes of rheumatoid arthritis.15 This estimated percentage was calculated by observing twins, especially identical twins who have the exact same genes. In fact, studies carried out on twins found further evidence that genes do contribute to the risk of developing rheumatoid arthritis.16 Identical twins share 100 percent of their genes, and it is more likely that both twins will have rheumatoid arthritis as compared to non-identical twins, who only share 50% of their genes.

The study found that both the twins had rheumatoid arthritis in 15 percent of the participating sets of identical twins in the study, while just four percent of non-identical twins had rheumatoid arthritis.17

Role of Age, Gender, and Ethnicity in Rheumatoid Arthritis

While rheumatoid arthritis can be found in people of every age, gender, and ethnicity, it has been found that nearly 70 percent of people with the disease are women.18 Most women with rheumatoid arthritis are commonly diagnosed between the ages of 30 and 60 years. It is believed that this high number of rheumatoid arthritis observed in women is due to female hormones. Men, on the other hand, are typically diagnosed later in life, and their overall risk of developing rheumatoid arthritis increases with age.

Pregnancy and Risk of Rheumatoid Arthritis

A study carried out by the American Society of Human Genetics discovered that women who are pregnant with babies that have the genes associated with rheumatoid arthritis are much more likely to develop rheumatoid arthritis themselves.19 Examples of this include babies that are born with the HLA-DRB1 gene.

This is so because, during pregnancy, a certain number of fetal cells get left behind in the mother’s body itself. Some of these remaining cells also have DNA present. Having fetal cells left behind with DNA present in them is known as microchimerism.20 These leftover fetal cells have the potential to alter the existing genes in the mother’s body. This is also one of the reasons why women are more likely to develop rheumatoid arthritis than men.

Behavioral and Environmental Risk Factors for Rheumatoid Arthritis

Behavioral and environmental risk factors are also known to play a massive role in the likelihood of developing rheumatoid arthritis. For example, it has been found that smokers have a higher risk of developing the disease, and smokers who already have the condition experience more severe symptoms of rheumatoid arthritis.21

Some of the other risk factors also include what type of oral contraceptives you are using or if you have undergone hormone replacement therapy. There is also a link between having a history of irregular menstruation cycles and developing rheumatoid arthritis. Women who have given birth or who breastfeed are known to have a lowered risk of having rheumatoid arthritis.

Some other behavioral and environmental risk factors that can attribute to rheumatoid arthritis include:

  • Obesity
  • Exposure to insecticides/pesticides
  • Exposure to air pollution
  • Occupational exposure to silica and/or mineral oil
  • Emotional or physical trauma/stress

Environmental or behavioral risk factors are modifiable because you can change and lower your risk by changing your lifestyle. Losing weight, reducing stress, quitting smoking, changing your occupation, and other such steps can reduce your risk for rheumatoid arthritis.

Conclusion: Is Rheumatoid Arthritis Hereditary?

No, rheumatoid arthritis is not hereditary, but your genetic makeup can increase the likelihood of developing rheumatoid arthritis. Researchers have found many genetic markers that are known to increase the risk of rheumatoid arthritis. These genes are associated with chronic inflammation, immune system response, and some of the symptoms of rheumatoid arthritis. However, it is essential to keep in mind that not everyone with these genetic markers goes on to develop the disease, and not everyone with rheumatoid arthritis has these genetic markers either.

This means that a person develops rheumatoid arthritis is usually because of a combination of various factors, including environmental exposures, behavioral and hormonal risk factors, and a genetic predisposition.

While some of these risk factors of rheumatoid arthritis are modifiable and can cut down your risk of developing this disease, but other factors cannot be changed, such as age and your genes.

However, leading a healthy lifestyle can help significantly reduce the controllable risk factors of developing rheumatoid arthritis. Some of the helpful steps you can take include:

  • Eating a well-balanced and nutritious diet.
  • Regular exercise
  • Quit smoking or restricting your exposure to secondhand exposure to cigarette smoke
  • Following healthy sleeping habits

Genetic risk factors are only responsible for just two-thirds of your risk of developing rheumatoid arthritis, and this risk is the highest if you have the specific HLA gene, which is associated with the disease.22

An early diagnosis and treatment of rheumatoid arthritis can help slow down the progression of the disease and help you manage the symptoms. This is why it is best to consult your doctor at the earliest if you suspect you might be having rheumatoid arthritis. While there is no cure for rheumatoid arthritis, there are many treatments and medications that help you manage your symptoms and improve the overall quality of your life.

References:

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  2. McInnes, I.B. and Schett, G., 2011. The pathogenesis of rheumatoid arthritis. New England Journal of Medicine, 365(23), pp.2205-2219.
  3. Rheumatology.org. 2020. Diseases And Conditions Rheumatoid Arthritis. [online] Available at: <https://www.rheumatology.org/I-Am-A/Patient-Caregiver/Diseases-Conditions/Rheumatoid-Arthritis> [Accessed 26 October 2020].
  4. Writer, R., 2020. Global Increase In Rheumatoid Arthritis Prevalence Rates And Disease Burden – Rheumatology Advisor. [online] Rheumatology Advisor. Available at: <https://www.rheumatologyadvisor.com/home/topics/rheumatoid-arthritis/global-increase-in-rheumatoid-arthritis-prevalence-rates-and-disease-burden/> [Accessed 26 October 2020].
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  9. Gonzalez-Gay, M.A., Garcia-Porrua, C. and Hajeer, A.H., 2002, June. Influence of human leukocyte antigen-DRB1 on the susceptibility and severity of rheumatoid arthritis. In Seminars in arthritis and rheumatism (Vol. 31, No. 6, pp. 355-360). WB Saunders.
  10. Arthritis.org. 2020. [online] Available at: <https://www.arthritis.org/about-arthritis/types/rheumatoid-arthritis/causes.php> [Accessed 27 October 2020].
  11. Remmers, E.F., Plenge, R.M., Lee, A.T., Graham, R.R., Hom, G., Behrens, T.W., De Bakker, P.I., Le, J.M., Lee, H.S., Batliwalla, F. and Li, W., 2007. STAT4 and the risk of rheumatoid arthritis and systemic lupus erythematosus. New England Journal of Medicine, 357(10), pp.977-986.
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