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Did My Genes Cause My Autoimmune Conditions?

As we are rapidly learning, autoimmune diseases appear to be a result of an unclear combination of genetics, environment and immune regulatory problems.  While we don’t completely understand the contribution of each in terms of proportions and impact, researchers have been somewhat successful in starting to put the pieces of the genetic puzzle together.  (This is also occurring regarding environmental impacts, though this is beyond the scope of this article.)  Here we take a look at some of the important genetic findings studies have yielded in terms of how our DNA contributes to the emergence of autoimmune disease.

Give me a quick overview of how much genes play a role in autoimmune disease onset?

This is a tough question to answer except to say that genes definitely seem to play a major role in this regard.  This is evidenced by the sheer number of gene locations that have been linked in some way to autoimmune disorders.  This genetic table on offers a list of genes connected to individual autoimmune conditions, which you might find helpful.

As with so many other disorders in medicine, the exact nature of genetic influence and how much it accounts for in terms of disease formation is presently still very much a mystery.  But, that mystery does seem to be unfolding slowly.  It does appear thus far that a combination of genes and environment is required for these diseases to manifest.  Beyond that, we are still working out the particulars.

For an overview of our current understanding of genetic factors in autoimmune disease, this page from the NIH covers the topic quite well.  It’s clear from these and other sources that autoimmune conditions are most certainly inheritable (though not always passed on and/or activated) – confirmed through twin studies and clinical observation within families.  Researchers have also discovered that while some genes promote development of disease, others serve protective functions.

What is the HLA gene family and what’s known about its connection to autoimmune disease?

The HLA (Human Leukocyte Antigen) genes are the human version of a gene group found more widely in nature, called the MHC (Major Histocompatibility Complex), which reside on chromosome 6 and code for something called cell surface proteins.

As it sounds, these are proteins that reside on the outside of a cell, and which can therefore function as antigens or present antigens to the immune system for assessment.  In those affected by one or more of the HLA genes, the body may not recognize the corresponding proteins (or the antigens they present) as native, which of course stimulates an autoimmune response.

The HLA gene family (known as “loci”, for their locations on chromosome 6) has been extensively studied in terms of their relationship to autoimmune conditions.  Classified into three MHC groups, class II appears to have the most impact on autoimmune conditions.  Though our understanding of this group of genes still leaves us short of being able to develop effective treatments at the moment (at least clinically, for the most part), the ongoing research and impressive rate of discovery leaves us with great hope for the near future.

Some common examples of HLA genes that have been correlated with and implicated in autoimmune disease include:

  • HLA-DQ2 (celiac disease)
  • DQ8 (celiac disease)
  • HLA-DR3 (type 1 diabetes, lupus, Sjogren’s and hepatitis)
  • HLA-DR4 (diabetes and rheumatoid arthritis)
  • HLA-DR2 (lupus)
  • HLA-B27 (ankylosing spondylitis, gonococcal arthritis, uveitis)
  • HLA-B47 (21-hydroxylase deficiency)

What is the IL gene family and what is known about its connection to autoimmune disease?

As with the HLA family above, the IL genes code for a group of proteins known as “interleukins” which are a type of “cytokine”.  (I mention these terms because many with autoimmune conditions may be familiar with them.  Other cytokines that you may have heard of include tumor necrosis factor (TNF) and the interferons.)

These proteins are inflammatory mediators (among other things) that act as messengers within the body and cells, promoting and regulating our immune responses.  When they act inappropriately against the self, inflammation of various organs is the result.

Some of the conditions affected by variation in the IL gene family are:

With the case of ankylosing spondylitis here, it is common for more than one gene at different locations (e.g. IL and HLA) to code for some part of the same disorder(s).

Are there other genes that are known or thought to be connected to autoimmune disease?

There are dozens if not hundreds of genes and gene families that have been correlated with various autoimmune diseases.  While an expansive look at these genes is beyond the purpose of this article, let’s take a quick look at a few of the better-known examples.

Other genes connected to autoimmune diseases include are below, with links to NIH and other academic studies:

  • SIAE – keeps B cells and antibodies within normal limits (i.e. mutation can lead to various autoimmune diseases via overproduction and hyper stimulation of these immune components).
  • P53 – leads to cell death, conferring protection against autoimmune disease; decreased in autoimmunity (meaning immune cells survive longer than they should and are thus less controlled)
  • MTHFR – various disorders possibly linked, but also found to be potentially protective in Grave’s disease
  • CTLA4 – inhibits T cell response and possibly leads to autoimmune disease when dysfunctional
  • NOD2 – connection unclear, but correlated with Crohn’s risk
  • PTPN22 – connected to susceptibility to many different autoimmune conditions; researchers are very excited about the possibility of having discovered a gene that may be used in the future to minimize the risk of developing so many disorders

This list is of course far from exhaustive and merely provides some examples of other genes that have been discovered and are now being researched for their connections to autoimmune disorders.  More information can be found at many of the links provided above.

Questions for your doctor:

  • How do I know if I’m a carrier for any of these genes/mutations?  What do my individual gene mutations mean in terms of clinical disease?
  • Should my spouse/children or I be tested genetically to see if we carry genes that pose additional risk?
  • If we discover that I am affected by autoimmune disease as a result of genetic mutations, what if anything can be done about it?
  • Can you suggest a good source of information for autoimmune genetics and/or specifics on my genetic risk factors?
  • What type of specialist might I consult with for any further questions about this issue?  Is there such thing as a rheumatologic geneticist or similar?

About the Author
Dr. Rothbard is a professional medical writer and consultant based in New York City, specializing in medical education articles targeted at a variety of audiences, from children through clinicians.  After leaving medicine, he worked as a biology and medical science educator for several years, before deciding to pursue writing full-time.  He may be reached at

This blog post was originally published by, written by Dr. Rothbard, and first published on Jul 17, 2014.

This post contains the opinions of the author. Autoimmune Association is not a medical practice and does not provide medical advice, diagnosis, or treatment. It is your responsibility to seek diagnosis, treatment, and advice from qualified providers based on your condition and particular circumstances. Autoimmune Association does not endorse nor recommend any products, practices, treatment methods, tests, physicians, service providers, procedures, clinical trials, opinions or information available on this website. Your use of the website is subject to our Privacy Policy.

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