Potential Causes and Risk Factors

Although the cause of RA is unknown, a leading explanation for why RA and other autoimmune disorders develop is that some environmental exposure or other non-genetic factor triggers the disease in individuals who are already genetically susceptible.1


Environmental exposures and non-genetic factors that may trigger RA?

What is meant by an environmental exposure or non-genetic factor? This covers a broad range of things, including substances that we encounter in our daily lives, our constitutions (hormones, body weight), medical procedures we have had, or lifestyle factors. The list includes viruses and bacteria, hormonal changes that occur during stress, and exposure to chemicals.

Cigarette smoke is recognized as a factor that increases risk for developing RA. Certain micro-organisms (bacteria) in the gastrointestinal tract have been linked to the production of auto-antibodies that attack the synovial joint tissue in RA. These bacteria, including one called Porphyromonas gingivalis, are present in the mouths of both people who smoke and those who have periodontal disease.1

Some factors that have been examined in relation to RA are specific to women. For instance, women who are taking oral contraceptives have a lower risk of developing RA than those who are not currently or have never taken oral contraceptives.1


How large an impact do environmental and other factors have?

Results from twin studies have estimated that genetics may account for up to 60% of the risk for developing RA. Therefore, environmental and other factors are likely to account for the remaining 40%. However, there is a relatively small body of research examining the influence of environmental and non-genetic factors on risk for developing RA. This is due, largely, to the difficulty of conducting studies examining these factors.2

To date, there is a relatively large body of evidence linking environmental exposures including cigarette smoke and silica dust to increased risk for RA. Other environmental  and non-genetic factors that have been examined with less conclusive findings include mineral oils and other substances known to affect immune system functioning, infectious agents, medical interventions (blood transfusions, medications), dietary factors, socioeconomic factors, and constitutional factors (weight, hormonal levels, fertility).2,3


Environmental and non-genetic factors and risk for RA

Exposures with established link

Cigarette smoking

Silica dust exposure (from mining)

Exposures and other factors without conclusive evidence

Mineral oils and other agent that influence immune system function

Infectious agents (bacteria, viruses)

Constitutional factors (hormonal, fertility, breast-feeding, weight

Dietary factors (food, vitamins)

Medical interventions (hormonal treatments, blood transfusions, surgery

Socioeconomic factors (occupation, income)


How do our genes contribute to RA susceptibility?

While research suggests that RA is not directly inherited, genetics does appear to play a role in predisposing or increasing a person’s chances for developing RA. Just as our DNA, which we inherit from our parents, determines whether we have blue or brown eyes or whether we are tall or short, our genes influence the way our immune systems operate. Experts believe that people who develop RA inherit something in the genes involved in the formation and operation of our immune system that increases the likelihood that the immune system will attack healthy tissue in the joints. In fact, genetic studies have identified certain variations inside common immune system genes that are more likely to be present in people who have RA.4

Results from genetic studies, including twin studies, family studies, and genome-wide linkage studies, have shown that heritability (or the genetic material that we inherit through our parents and family) definitely contributes to the chances of developing RA. Twin studies are an effective way of examining the role of genetics in diseases. These studies are based on the principle that if a disease is purely genetic (100% heritable), you would expect that identical twins (also known as monozygotic twins), who share all the same genes, would both develop the disease. One analysis of data from twin studies found that genetics accounted for over 60% of the difference between people who develop RA and those who do not. In other words, according to these analyses genetics has a pretty strong influence on the development of RA.5

Genetic studies using advanced computer technology to scan the entire genome have identified genetic variations that may increase a person’s susceptibility for RA. Results from these studies have located variations in several genes involved in the function of key immune system cells and chemical, including T lymphocytes (T cells), tumor necrosis factor (TNF), complement, and auto-antibodies.4

Written by: Jonathan Simmons | Last reviewed: September 2013.
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