Rheumatoid Arthritis Genetic Discoveries

I got a link to a short interview called GeneTalk with 23andMe: Rheumatoid Arthritis with a key researcher on RA and genetics. Even though it was just an overview, the topics were fascinating. Free sign up may be required to read the full article, but I’ll quote it directly here.

Are there genes that bring a risk for Rheumatoid Arthritis?

Balloon liftoffExcerpt: “23andMe spoke with Peter K. Gregersen, M.D. about the complex interaction between genes and environment—and how this may affect a person’s risk of developing RA. Over the past decade, Dr. Gregersen has directed the world’s largest effort to identify the genes underlying RA, and he is internationally recognized as a leading investigator in the genetics of autoimmune disorders. In 2004, Dr. Gregersen and his colleagues identified PTPN22 as the first major gene that confers risk for multiple autoimmune diseases—a discovery that provided direct evidence that diverse forms of autoimmune disease are related genetically. Definitive evidence for the existence of additional risk genes for RA emerged from Dr. Gregersen’s laboratory in the last few years.”

What’s interesting here?

We are living in an exciting time. Of course patients want to see research for a cure for Rheumatoid Arthritis. However, the mystery and complexity of the Rheumatoid Arthritis disease process make that a more difficult prospect than most of us can fathom. That is why we ought to be keeping our eyes on genetic research that could provide clues about how RA works.

How much do genes increase Rheumatoid Arthritis risk?

Excerpt: “Dr. Gregersen: There is a genetic component to rheumatoid arthritis, and we know this because of a slight tendency for RA to cluster in families. For example, the risk to an identical twin of someone with RA is increased about 20-30 fold, and siblings are at about 3-10 fold increased risk. However, because RA is not that common in the population (~0.5% or 1 in 200 people), the absolute risk to siblings is still fairly low. There are clearly other environmental factors, such as smoking, that also increase risk for RA. We don’t yet have a full understanding how genes and environment interact to cause this disease. We have known for over two decades about a group of genes on chromosome 6 called HLA genes that carry a moderate risk for developing RA.”

What’s interesting to us?

Articles vary in reporting prevalence of Rheumatoid Arthritis. Recent studies found RA to be more common than previously believed. It’s shocking how much we don’t know. Look at the range for risk of siblings: between three and ten times the risk? Not odds you could use to bet.

An explosive period of discovery for Rheumatoid Arthritis

Excerpt: “In most cases, we haven’t yet really established what the specific variation is that actually causes the increase in risk. We are currently in an explosive period of discovery, and I expect that a number of additional genes associated with RA will be discovered in the coming year or two. …It is interesting, however, that recent data suggests that the combination of cigarette smoking and having some of the riskier versions of genes associated with RA may put someone at quite high risk for some types of RA. This is particularly evident for a type of RA that is accompanied by antibodies to proteins that have been modified to contain the amino acid citrulline.”

What’s interesting?

There are “riskier versions of genes”?  There are “some types of RA”? These are not things that we learn from our rheum docs so I was glad to read this. A recent blog discussed the “citrulline” component to RA research.

Can gene risk be used to help people with Rheumatoid Arthritis?

Excerpt: “At this point, there are no clinically actionable steps that can be recommended based on a person’s genetic profile at these RA risk alleles. Despite the lack of immediate practical benefit for patients and families, I believe the coming discoveries in genetics are going to ultimately give us a much clearer picture of what is causing RA, which will allow us to diagnose and treat the disease much more effectively. There is also a big push on now to use both genes as well as other types of laboratory tests (such as antibodies and other blood measurements) to properly select drugs for people with RA.”

So, genetic tests could confirm RA diagnosis or disease severity

It’s not here yet, but genetic tests may be a key to earlier and more effective Rheumatoid Arthritis treatment. The things we discuss here on this site about (1) treatment that is as aggressive as appropriate for each the patient, (2) early examinations with rheumatology specialists, and (3) relying on more heavily upon patient measures of disease activity will all make more sense when there are medical tests that can confirm disease activity. However, those three principles will remain essential in order to obtain the tests.

Listen to Dr. Gregersen talk about genetic research for RA here on video.

Postblog: Indeed there are several new studies this year on genetics and Rheumatoid Arthritis. We cannot review them all here, but here is a link to another about predicting erosive Rheumatoid Arthritis disease / inflammatory polyarthritis.

Recommended reading:

Kelly Young

Kelly Young is an advocate providing ways for patients to be better informed and have a greater voice in their healthcare. She is the president of the Rheumatoid Patient Foundation. Kelly received national acknowledgement with the 2011 WebMD Health Hero award. Through her writing, speaking, and use of social media, she is building a more accurate awareness of Rheumatoid disease aka Rheumatoid Arthritis (RA) geared toward the public and medical community; creating ways to empower patients to advocate for improved diagnosis and treatment; and bringing recognition and visibility to the Rheumatoid patient journey. In 2009, Kelly created Rheumatoid Arthritis Warrior, a comprehensive website about RA of about 950 pages and writes periodically for other newsletters and websites. Kelly served on the Mayo Clinic Center for Social Media Advisory Board. There are over 42,000 connections of her highly interactive Facebook Fan page. She created the hashtag: #rheum. Kelly is the mother of five, a home-schooler, Bible teacher, NASA enthusiast, and NFL fan. You can also connect with Kelly by on Twitter or YouTube, or LinkedIn. She has lived over nine years with unrelenting Rheumatoid disease. See also http://www.rawarrior.com/kelly-young-press/

24 thoughts on “Rheumatoid Arthritis Genetic Discoveries

  • Pingback: Tweets that mention Prominent genetics researcher on RA: There's not much we can do to help yet. Don't smoke: -- Topsy.com

  • October 26, 2010 at 2:09 pm
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    Very exciting things to look forward to. I wish I could be take part in gene studies, but we don’t have a university hospital nearby.
    I see the writing on the wall having smoked in the past and having high anti-ccp antibodies. It’s unfortunate I didn’t know. I have warned a niece of mine, and hope she listens. I quit 12 years ago and only smoked part time. RA came along about 4 yrs ago.

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    • October 26, 2010 at 2:12 pm
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      Ronda, that site I linked to 23 and Me, seems to have some kind of a registry you might be able to join. I haven’t had time to look into it, but I know one doc who has done research I saw on their site, so I believe it’s legit. Lmk what you think of that option.

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      • October 26, 2010 at 8:37 pm
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        From what I can see you can register to support a study on the disease of your choice. You have to buy a DNA test. Once they get a 1000 supporters for a disease, then they do a study based on the the DNA and survey results of participants. I did see an article last year in Arthritis today magazine on DNA tests and 23andMe. I found it interesting and looked at the site back then. I would love to do it, but $400-500??

        Reply
  • October 26, 2010 at 4:22 pm
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    This makes me wonder. If regular mammography screening is encouraged why not a “regular RA screening”? It seems that every individual – women in particular – could benefit from a onetime “genetic RA panel” once they reach a certain age as well as regular screening for key inflammation / RA markers if they are found to be in the “genetically-risky” group.

    Is this idea just too crazy?!

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  • October 26, 2010 at 8:16 pm
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    I believe one hundred percent its in the genes. My father has it. I have a twin sister, and we both have it. We were diagnosed about a year apart. And my daughter has it as well. All of us were told that it is genetic related. Keep up the good work.

    Reply
  • October 26, 2010 at 8:22 pm
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    It would be a wonderful thing if there were a blood test for RA, I constantly worry and pray for my children and grandchildren that they won’t inherit this awful disease, it is really worse that heart disease, which also runs in my family! A heart valve problem can be repaired, irregular heart rates can be fixed with a pacemaker~~~but RA-NO KNOWN CURE, very little pain relief, it just takes over your life, one day at a time. Every once in a while, it will let you have a glimpse of a normal life, but it will grab it back with a flare worse than you can ever imagine! Sorry to sound so grim, but I just went for that ride 🙁 Thought I was truly in remission, had a couple months pain free then WHAM, it hit me with a ton of bricks, back to square one! Pain medication, chills, missings activities, church, unable to care for myself & unrelentless pain. I could go on and on and on, but I think I will stop now. Good night and pain free hugs to all! 🙂

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    • October 26, 2010 at 8:32 pm
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      I would just like to give you hug if I could. Right now I feel like Im in remission an I know I will be hit to with a big wake up call. Im not on any meds right now because my husband lost his health insurance and I have a 3,000 co-pay for my orencia treatment. So I decided not get it till he gets his insurace back and that will be in decemeber. I hope I last that long. Hope you have a great pain free night

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      • October 28, 2010 at 9:11 am
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        Try contacting the manufacturer of your medication. Most have some financial assistance for patients in need.

        Reply
  • October 26, 2010 at 10:27 pm
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    I pray for my children’s sake they come up with something quick. Then they could get treated early if they end up having it. Interestinly, I”ve never smoked but I grew up in a smoking family, from my grandmother to my little sister. Holidays at our house looked like a smoky pool hall!

    Kelly,
    Thanks again for all the research you do. You keep us all armed with knowlege. You are the best ammo ever!

    Reply
    • October 26, 2010 at 10:43 pm
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      Me too, there was a lot of smoke in my house – and car. And I remember complaining. 😛

      Reply
      • October 27, 2010 at 1:00 am
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        I never smoked around my children, could not have done that ever. On the other hand my husband grew up around smokers in his house and is healthy. He chewed tobacco for 35 years and smoked some too. His grandpa had RA so he is also at genetic risk. I grew up in a smokeless environment with no known genetic risk. I only smoked about 3 cigs a day and quit when I was pregnant, nursing or any time it didn’t work. Who knows?

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        • October 27, 2010 at 4:45 pm
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          Sounds like I took in more 2nd hand smoke than you took 1st hand! :O It was pretty constant for my first decade & I remember being ill inside of the car a lot with the windows up.

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          • October 27, 2010 at 9:34 pm
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            UGH, that’s awful, no one knew back then. It seems like common sense would tell them it can’t be good.

  • October 28, 2010 at 3:54 pm
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    We already know that different RA treatments work for every patient. I’m thinking–hoping really–that this genetic research will, at the least, show that certain treatments work for certain genotypes of the disease. That would mean by running a genetic test, your doctor would be able to tell immediately what drugs you need to fight YOUR RA.

    I’m very interested in modes of inheritance, too. No one in my family, either side, has ever been diagnosed with RA…but we have a family history of lupus. Will this research suggest that family history of any autoimmune disease puts you at risk for the others?

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    • October 28, 2010 at 9:11 pm
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      Maybe someday they might have a genetic test similar to the BRAC analysis for breast cancer risk. But that kind of testing only tries to quantify your potential risk, they’re not linked to treatment.

      With a disease like RA it is your adaptive immune system (B cells and T cells) that is causing the problem. These respond to some antigen from the environment and they go a little “nuts”. Perhaps your genes can make these more suseptible to going “nuts”, but it is a gene/environment interaction that is the likely culprit. Decoupling the environment effect from the gene effect is very difficult. Maybe someday, but I don’t know of a technology exists to do this yet. Craig Venter of Celera Genomics is one of people credited with being the first to sequence the human genome. As a matter of fact, his genome is on the internet for all to see. In a recent interview he said that with our current level of knowledge, you couldn’t even tell what color his eyes are by looking at his genetic code. I think that statement speaks volumes to our current level of knowledge.

      I think the next biggest thing for RA might be a diagnostic test to predict outcomes and/or direct treatments, much like HercepTest to identify breast tumors that overexpress the HER2 protein to direct treatment with herceptin. Wouldn’t it be great if they could biopsy some of our synovial fluid or synovium or take some blood and be able to know if you’d respond, for example, to a TNF drug or not. Think of the time and money and injections/infusions and side effects that we could be spared if we knew a drug wouldn’t work. Or if you knew it would work, you could go on a treatment with more courage.

      Reply
  • October 29, 2010 at 3:49 pm
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    All this is very interesting to me. My mother had SEVERE RA. Her mother had gouty arthritis. My father’s sister had pretty bad RA (nothing like my Mom’s). I had paradoxical arthritis for 30 years before I was diagnosed with RA. Now my 41 yo daughter is complaining of migratory joint pains, mostly focused in her wrists and feet. She has inadequate health coverage to go to a rheumatologist, and *thinks* she has no time to go even if I pay for it for her (full time work, full time school, full time wife & mother). I’m just beside myself. Now IF there were a gene test now, we would know what her risk-ratio is.

    All I can say is that knowing of the possibility of this test in the distant future is both a blessing and a curse!

    Elizabeth

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    • October 29, 2010 at 4:22 pm
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      I hope she goes Elizabeth. I know you know how important it is. A local friend of mine just lost her mom today to RA complications. She has it too. We do need someone to care & press forward harder. I know the science is behind, but to read the statistics about how little is being done in comparison with other more rare conditions just convinces me this is unacceptable.

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      • October 30, 2010 at 8:34 pm
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        Clinicaltrials.gov says there are 1082 studies in their database that mention RA. I can’t divulge the statistic on the current number of NMEs that I’ve seen presented but I tell you there are several dozen new molecules currently being evaluated for RA. Maybe the dollars spent per patient is a bit low compared to other diseases, but perhaps we’re getting more bang for our buck.

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        • October 30, 2010 at 10:16 pm
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          Hi RaRAP, I hope you are doing well. I knew this had been discussed before so I went to find where. My friend Carol ran a search on how many studies in that same database are actually on RA. She came up with 295 as opposed to almost 4,000 for breast cancer. Do you think her search was flawed? Not sure what you meant by “mentioned RA” in the studies on your list. I hope you’re right & the picture is not as bleak as the numbers show. Dollars spent are a bit low yes when the ACR says 25$ is spent per patient on RA and $330 per patient for rarer diseases like Lupus or MS or type 1 diabetes. This is truly the back of the bus “hopeless” disease in the minds of many. I have read that no cure is possible in our lifetime. If I accept that, I can still fight that they might search for one for my children who carry so many of my genes.

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          • October 31, 2010 at 12:30 am
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            I’m doing ok. I’m a little apprehensive about trick-or-treating with the kids tomorrow night as my knees are hurting pretty bad. It is getting colder here and that seems to be making my pain and stiffness worse.

            I just went to clinicaltrials.gov and did a search on rheumatoid arthritis. Anyone can do this, give it a try. Now let me preface that the 1082 number are not all drug trials. I didn’t look through all the studies, but it’s likely that the smaller number you cite represents the new drug trials.

            While it may be “back of the bus” to some, I know it is front and center to many others. Perhaps your ACR meeting trip will change your opinion. There are people out there fighting for us.

            There is always hope for a cure, but to be realistic how many diseases can we actually cure. We can treat and manage and improve life expectancy and quality of life, but cures are rare. You don’t lose until you give up and we won’t give up.

          • October 31, 2010 at 9:14 am
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            Thanks. Take it easy on your knee. I don’t need to be convinced there are great researchers out there!! Reading the abstracts & articles of the good guys is kinda exciting for patients who do that (I know some of our readers do it). I wonder if I’ll get to meet any of my favorites. I just heard 14,000 docs attend? Can that be right?

          • October 31, 2010 at 1:15 pm
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            14,000 is entirely possible. So if your favorites are there and you can find them you’ll definitely be able to meet them. If they’re not speaking they’ll be milling around the crowd just like you. If there is someone you really would like to meet with try and get a hold of them prior to the ACR meeting and ask to meet while you’re there.

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