A popular pastime for many older people is to try and figure out their chances of getting one ailment or another. Mayo Clinic researchers have simplified it – they have figured out the lifetime risk of developing rheumatoid arthritis and six other autoimmune rheumatic diseases for both men and women. “We estimated the lifetime risk for rheumatic disease for both sexes, something that had not been done before — separately or collectively,” says Cynthia Crowson Mayo Clinic biostatistician and first author. “Prevalence and incidence rates existed, but prevalence figures underestimate individual risk and incidence rates express only a yearly estimate.”
The researchers were looking for an accurate basis to offer an easy-to-understand average risk over a person’s lifetime, knowing that risk changes at almost every age. They used data from the Rochester Epidemiology Project, a long-term epidemiology resource based on patients in Olmsted County, Minn. The cohort of 1179, consisted of patients diagnosed between 1955 and 2007, allowed the team to extrapolate the nationwide estimates.
The adult lifetime risk in the United States of having some kind of inflammatory autoimmune disease is 8.4 percent for women and 5.1 percent for men. Based on year 2000 population figures, that means one woman in 12 and one man in 20 will develop one of the conditions in their lifetime. The authors consider that a substantial risk and say their findings should encourage more research on the value of early diagnosis and intervention for people with increased genetic risk of arthritis. They hope the new figures will help in counseling patients and in fundraising efforts to find improved treatments.
The research was supported by the National Institutes of Health.
Smoking accounts for more than a third of cases of the most severe and common form of rheumatoid arthritis, indicates research published online in the Annals of the Rheumatic Diseases. And it accounts for more than half of cases in people who are genetically susceptible to development of the disease, finds the study.
The researchers base their findings on more than 1,200 people with rheumatoid arthritis and 871 people matched for age and sex, but free of the disease. The patients came from 19 health clinics in south and central Sweden, while their healthy peers were randomly selected from the population register. All the participants were aged between 18 and 70. They were quizzed about their smoking habits and grouped into three categories, depending on how long they had smoked. Blood samples were taken to assess all the participants' genetic profile for susceptibility to rheumatoid arthritis and to gauge the severity of their disease, as indicated by their antibody levels.
More than half of those with rheumatoid arthritis (61%) had the most severe form of the disease, which is also the most common form, as judged by testing positive for anticitrullinated protein/peptide antibody (ACPA). Those who were the heaviest smokers – 20 cigarettes a day for at least 20 years – were more than 2.5 times as likely to test positive for ACPA. The risk fell for ex-smokers, the longer they had given up smoking. But among the heaviest smokers, the risk was still relatively high, even after 20 years of not having smoked.
Based on these figures, the researchers calculated that smoking accounted for 35% of ACPA positive cases, and one in five cases of rheumatoid arthritis, overall. Although this risk is not as high as for lung cancer, where smoking accounts for 90% of cases, it is similar to that for coronary artery heart disease, say the authors. Among those with genetic susceptibility to the disease, and who tested positive for ACPA, smoking accounted for more than half the cases (55%). Those who smoked the most had the highest risk.
The authors point out that several other environmental factors may contribute to an increased risk of rheumatoid arthritis, including air pollutants and hormonal factors. But they suggest that their findings are sufficient to prompt those with a family history of rheumatoid arthritis to be advised to give up smoking.
The idea that disease-causing genes can be beneficial is not new. The most clear-cut case involves a gene variant that, when present in two copies, causes sickle cell anaemia, which can result in severe pain, organ damage and death. Although it seems that natural selection would work to eliminate the disorder, the variant remains prevalent in some areas of Africa because people with just a single copy are less susceptible to malaria. Evolutionarily the trade-off is worth it: Far more people are protected from malaria than ever develop sickle cell anaemia even in today’s environment.
Unlike sickle cell anaemia, which is caused by a mutation in just one gene, many complex diseases are associated with several variants – specific locations in the DNA where the nucleotide ‘letters’ vary between individuals. These locations are known as SNPs, for single nucleotide polymorphisms. Some of these SNPs are associated with an increased disease risk, while others protect against developing the disease. When calculating an individual’s overall genetic risk, it’s necessary to consider the net effect of all of his or her variants.
Researchers at Stanford University picked seven well-known conditions to study: type-1 and type-2 diabetes, rheumatoid arthritis, hypertension, Crohn’s disease, coronary artery disease and bipolar disorder. Previous genome wide association studies have identified several hundred SNPs associated with each disorder. Corona found that of the top SNPs associated with type-1 diabetes, 80 have been recently increasing in prevalence, meaning that they underwent positive selection. Of these, a surprising 58 are associated with an increased risk of the disorder, while 22 appear protective. Similarly, SNPs associated with an increased risk for rheumatoid arthritis were found to be positively selected. In contrast to type-1 diabetes and rheumatoid arthritis, Corona found that we’re evolving away from a tendency to develop Crohn’s disease (that is, more protective SNPs than risky SNPs have been positively selected).
Results for the other three disorders – type-2 diabetes, coronary artery disease and bipolar disorder – showed that protective and risky SNPs were positively selected in about equal proportions. ‘Now we’re starting to see little hints as to why this might be the case,’ said Butte. For example, a recent study in another lab showed that genetic variations in an antiviral response gene called IFIH1 that improve its ability to protect against enterovirus infection (and the resulting severe, potentially deadly, abdominal distress) also increase a carrier’s risk for type-1 diabetes. And scientists who study global disease patterns have long noted that the prevalence of tuberculosis varies inversely with that of rheumatoid arthritis.
‘It’s possible that, in areas of the world where associated triggers for some of these complex conditions are lacking, carriers would experience only the protective effect against some types of infectious disease,’ said Butte, who pointed out that the cumulative effect of many SNPs in a person’s genome may buffer the effect of any one variant, even if it did raise a person’s risk for a particular condition.
Regardless of the reason, some evolutionary tenets still apply. Healthier people are, presumably, more likely to reproduce and pass those same genes – be they protective or risky – to their offspring. When conditions changed because of differences in diet, exposures or location as populations move around the globe, carriers of the risky SNPs began to develop the conditions we struggle with today.
Corona and Butte are now expanding their investigation to include even more SNPs and diseases. They are also looking at the genetic profile of various types of tumours to see if there’s evidence for positive evolutionary pressure there as well.
‘Even though we’ve been finding more and more genetic contributions to disease risk,’ said Butte, ‘that’s not really an appealing answer. There have got to be some other reasons why we have these conditions.’
Source: Stanford University Medical Centre
The new study comprised 366 people with RA from eight separate trials. Fasting followed by eating a vegetarian diet for 13 months or eating a Mediterranean style diet replete with fruits, vegetables, healthy fats, and legumes for 12 weeks may relieve pain, the study showed. These diets did not improve morning joint stiffness or physical function when compared to regular diets.
There was not enough data to draw any conclusions about how vegan and/or elimination diets affect RA symptoms.
The positive changes seen with vegetarian and Mediterranean diets may be a result of simply adapting a healthier way of eating as opposed to any specific diet, the study researchers conclude.
People with RA who were put on special diets were more likely to drop out of the studies, suggesting that some people may have difficulty adhering to the eating plans.
Some special diets also resulted in weight loss which may not always be a good thing people with RA who are already at risk for nutritional shortfalls.
“There is a need for more and better research on dietary interventions for RA,” conclude researchers led by Geir Smedslund, PhD, a senior researcher at the Centre for Rehabilitation in Rheumatology at the Diakonhjemmet Hospital in Oslo, Norway.