PTPN22 and Autoimmune Diseases

The body continually balances between fighting off dangerous pathogens and keeping the immune response in check. The PTPN22 gene plays a pivotal role in that balance, and genetic variants (SNPs) in PTPN22 increase your risk of autoimmune conditions such as vitiligo, alopecia, RA, type 1 diabetes, and autoimmune thyroid diseases.

PTPN22: Genetics and Autoimmune Diseases

Genome-wide association studies allow researchers to cast a wide net, searching for genetic variations that increase susceptibility to diseases or conditions. One of the first autoimmune-related variants that genetic researchers discovered is in the PTPN22 gene (protein-tyrosine phosphatase nonreceptor 22).

This unexpected discovery left researchers searching for the answer to ‘why PTPN22?'[ref][ref]

Subsequent research shows that PTPN22 regulates the immune system by impacting T cell activation and B cell auto-reactivity. It acts as a negative regulator, dampening T cell activation. Additionally, PTPN22 impacts innate immunity by promoting interferon I production.[ref][ref][ref]

A balancing act between killing invaders and not hurting your own cells.

The body produces T-cells and B-cells as part of the immune system. These are the cell types that recognize danger (e.g., bacteria, viruses) and identify non-danger (e.g., your own cells).

B cells (aka B lymphocytes) are a type of white blood cell that secretes antibodies and also presents antigens. T cells, similarly, are a type of white blood cell that matures in the thymus and controls immune response. Both B and T cells perform important immune system functions for determining invaders and keeping immune response in check against ‘self’.

Variants in the PTPN22 gene change the way that it functions, causing an increase in the inhibitory function of B-cells.[ref][ref]

The PTPN22 variants are linked to autoimmune diseases that affect connective tissues, the thyroid, joints, muscles, blood, and the pancreas. But the variants don’t seem to increase the risk of autoimmune diseases that target the eyes, gastrointestinal tract, or brain. PTPN22 genetic changes are linked to:[ref][ref][ref]

  • Rheumatoid arthritis
  • Vitiligo
  • Alopecia areata
  • Vasculitis
  • Autoimmune Addison Disease
  • Graves’ Disease
  • Hashimoto thyroiditis
  • Idiopathic inflammatory myopathy
  • Juvenile arthritis
  • Lupus
  • Systemic scleroderma
  • Type 1 diabetes
  • Myasthenia gravis
  • Allergic rhinitis

What if you don’t have an autoimmune disease?

Research shows that even people without autoimmune diseases have a change from the PTPN22 R620W variant. People with even one copy of the variant have increased autoreactive B cells and autoantibodies.[ref]


Recent work using transgenic mice points to the PTPN22 variant that increases autoimmune risk by possibly decreasing skin cancer risk and improving survival in other cancers.[ref]

Additionally, research seems to show that people with the PTPN22 variants are at a decreased risk of Crohn’s disease and Behçet’s disease.[ref]


PTPN22 Genotype Report:

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The rs2476601 R620W variant is a well-studied link to autoimmune diseases, with over 1,000 studies that reference it.

Check your genetic data for rs2476601 R620W (23andMe v4; AncestryDNA):

  • G/G: typical
  • A/G: increased risk of autoimmune diseases and endometriosis
  • A/A: increased risk of autoimmune diseases including: vitiligo[ref], Graves’ disease, type 1 diabetes[ref], Meniere’s disease[ref], juvenile arthritis[ref] psoriasis[ref] endometriosis[ref]

Members: Your genotype for rs2476601 is .

Check your genetic data for rs6679677 (23andMe v4, v5;):

  • A/A: Increased susceptibility to autoimmune diseases including: Hashimoto’s thyroiditis[ref], type 1 diabetes[ref], juvenile arthritis[ref]
  • A/C: increased risk of autoimmune diseases
  • C/C: typical

Members: Your genotype for rs6679677 is .

Check your genetic data for rs1310182 (23andMe v4; AncestryDNA):

  • G/G: Somewhat increased susceptibility to autoimmune diseases including: allergic rhinitis[ref], ulcerative colitis[ref], type 1 diabetes[ref]
  • A/G: typical risk
  • A/A: typical

Members: Your genotype for rs1310182 is .



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About the Author:
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering and also an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.

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