4 Genetic Tests That Can Help Individualize Treatment Options for Patients With Autoimmune Disease

Autoimmune diseases impact a whopping one in ten individuals, and the frequency of these chronic conditions is still on the rise. While there is still much to learn when it comes to the underlying physiology of autoimmune conditions, it is clear that a complex interplay between genetics, immune system function, and environmental factors is a common theme with autoimmunity.  

When an autoimmune disease impacts an individual, their immune system begins to attack their own tissues, whether it's the joints, the thyroid, or another area of the body. Roughly 80% of all autoimmune conditions affect women, making it apparent that genetic differences between men and women may be a part of the bigger picture around the pathogenesis of these conditions. Genetics is only part of the story regarding autoimmune diseases, but evaluating genetics can be a helpful piece of a bigger, holistic functional medicine approach to managing these complex conditions.  

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What are Genetics?

The scientific field of genetics is a branch of biology that studies genes and heredity, or how certain traits are passed down from generation to generation based on DNA. Specific changes at certain locations on DNA strands - called genetic SNPs or single nucleotide polymorphisms - can provide insight into risk factors for various health conditions, including the development of certain autoimmune diseases.  

Current DNA testing methods used by functional medicine providers can show some of these areas of higher risk. While genetics can play a role in health, they are really a part of a larger picture that includes your environment, lifestyle, nutrition, and stress levels. It's crucial to look at the entire picture regarding health and the risk of developing chronic diseases.

What is The Definition of Autoimmune Disease?

Autoimmune diseases are medical conditions that result from the immune system accidentally attacking your own body instead of protecting it. These conditions can affect various tissue types in the body and cause various symptoms, many of which are general and non-specific, making diagnosis difficult. Symptoms of autoimmune conditions may include fatigue, chronic pain, nausea, and headaches, to name a few. In an autoimmune flare, the body struggles to distinguish between "self" and "non-self," producing autoantibodies against normal, healthy tissue by accident.  

There are currently more than 100 known autoimmune diseases, which likely result from interactions between genetics and environmental factors. Gender, race, and ethnicity have also been linked to the likelihood of developing an autoimmune condition. Environmental impacts such as ultraviolet radiation, agricultural chemicals, heavy metals like mercury, and nutrition can all affect autoimmune disease development.  

The Role Of Genetics In Autoimmune Diseases

According to Johns Hopkins University, three primary factors are at play in developing autoimmune disease: genetics, the immune system, and an individual's environment. The genes may provide the "predisposition" to developing an autoimmune condition, while the environment delivers the triggers that set the condition into motion via dysregulation of the immune system.

While genes may only be part of the story when it comes to autoimmunity, it's worth considering genetics in a functional medicine approach to managing these conditions due to the power of epigenetics. Epigenetic modifications - which can occur due to nutrition, lifestyle, stress management, and environment - impact how a given gene is expressed, and these epigenetic changes have also been linked to autoimmune development. The power of epigenetics makes it clear that, in many cases, our lifestyle and environment can impact how the genes we are born with function and thus impact autoimmune pathophysiology as well.  

Ultimately, while the presence of certain gene SNPs might predispose an individual to a higher chance of autoimmune disease development, understanding the big picture of the interplay between genes and lifestyle/environment factors is essential. There's still much to be uncovered about how specifically these genes impact autoimmunity progression.

Which Autoimmune Diseases Have a High Correlation With Genetics?

While there may be many more autoimmune diseases linked to genetics, the following conditions have been researched and have shown a high correlation:

Rheumatoid Arthritis

Rheumatoid Arthritis, or RA, is a type of autoimmune disease that mainly impacts the smaller joints of the feet and hands, and it's estimated that it has a 60% heritability chance. Multiple genes may play a role in the development of RA, alongside environmental and lifestyle factors. The most significant genes that have been studied in relation to RA are the Human Leukocyte Antigen genes or HLA genes. The HLA-DRB1 allele, in particular, has been well-studied and contributes to about 1/3 of the genetic component of RA development.  

Hashimoto's Thyroiditis

Hashimoto's Thyroiditis is an autoimmune condition that impacts the thyroid gland and often results in hypothyroid symptoms such as fatigue, constipation, hair thinning, weight gain, and more. It's common to see this condition appear within families, implying that there is a hereditary component. Several genes have been linked to autoimmune thyroid conditions, including a higher prevalence of MTHFR mutations, which can impact various inflammation and metabolic pathways. Additionally, HLA genes and other immunoregulatory genes have also been proposed in research to play a role in the development of Hashimoto's Thyroiditis.

Celiac Disease

Celiac disease is a multifactorial autoimmune disease that involves an immune response to the gluten protein, leading to significant damage to the small intestine and difficulty absorbing nutrients from food. Many people with Celiac disease will have one of two HLA genes, HLA-DQ2 or HLA-DQ8, that make them more likely to mount an immune response against gluten.

Crohn's Disease

Crohn's disease is a kind of IBD (inflammatory bowel disease) in which the immune system can attack different areas of the bowel, most often the small intestine. This can lead to pain, gastrointestinal symptoms, and malabsorption. An interplay between genetics and environmental factors underlies the disease's development, with individuals with certain genetic predispositions having a higher likelihood of environmental factors triggering immune system dysregulation. The most well-studied genes that play a role in Crohn's disease include NOD2, IL23R, and ATG16LI genes. These genes tend to cause an increase in pro-inflammatory reactions in the body and, in the case of NOD2, may impede the clearance of bacteria from the body, which can further stimulate inflammatory signaling pathways.  

Multiple Sclerosis

Multiple Sclerosis is an inflammatory condition of the CNS (central nervous system) that results in progressive degeneration of neurons. The incidence of MS is higher in family members of affected individuals, with potentially over 200 implicated genes in disease development. HLA genes, particularly HLA-DRB1, have the most evidence of playing larger roles in MS.

Type 1 Diabetes

Type 1 Diabetes (T1D) typically appears in adolescence and impacts the insulin-producing cells of the pancreas. Having a family member with T1D and having certain HLA genotypes results in a 1 in 5 chance of developing the condition, while having the HLA genotypes alone results in a 1 in 20 chance. These risk percentages suggest that certain HLA genotypes increase the likelihood of disease development, but other hereditary components may play a role as well.

Genetic Tests for Patients Concerned About Autoimmune Disease

Functional medicine laboratory testing can evaluate a person's genetics as part of a holistic approach to managing autoimmune disease. It's important to look at nutrition and lifestyle as well since genetics are only a piece of the puzzle in looking at these conditions.  

3X4 Genetics

One of the most comprehensive genetics tests is the 3x4 Genetics Test, which looks at over 134 genes related to inflammation, detoxification, immune regulation, and more. This panel includes many of the genes already discussed above, including MTHFR and HLA genes, as well as additional genes related to enzyme production, antioxidant capacity, detoxification ability, and other important metabolic functions to evaluate when assessing autoimmune disease risk and progression.  

DNA Risk

Comprehensive genetic profiles like the DNA Risk panel evaluate HLA gene variants that have been linked to common autoimmune conditions, such as RA, Crohn's disease, Celiac disease, Multiple Sclerosis, Type 1 Diabetes, and others. Such a panel can provide insight into individual risk as part of a "big picture" functional medicine evaluation.  

MTHFR Evaluation

Assessing for MTHFR mutations can be part of a broader functional medicine approach to evaluating autoimmune disease management and risk. MTHFR mutations potentially play a role in the development of several autoimmune conditions, including Hashimoto's Thyroiditis and Multiple Sclerosis.

CICIA Genetics

The CICIA Genetics screen evaluates genes specifically related to Celiac disease and Crohn's disease and can help an individual in determining their risk for these specific autoimmune conditions. This screening tests for HLA genes as well as NOD2 and ATG16LI, which are two of the most widely implicated genes in the etiology of Crohn's disease.

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Summary

Autoimmune diseases have complex etiologies and often result from a combination of genetic predisposition, various environmental triggers, and other lifestyle factors that impact immune system regulation and inflammation. Looking at genes related to autoimmune diseases is a piece of a broader, "big picture" approach to managing these complex conditions using functional medicine. Understanding genetic risk can help to identify lifestyle changes to support optimal health, making an impact on the factors that an individual can control, such as nutrition, stress management, and environment.