PTPN22 R620W — broad autoimmunity risk variant
One copy of the PTPN22 R620W variant detected.
You have one copy of a DNA change in PTPN22 that subtly nudges several autoimmune risks up.
Associated with modestly elevated lifetime risk of several autoimmune conditions including type 1 diabetes, rheumatoid arthritis, lupus, and Hashimoto's thyroiditis. Effect on any single condition is small.
Your lifetime odds of several autoimmune conditions — type 1 diabetes, rheumatoid arthritis, lupus, and a thyroid condition called Hashimoto's — are slightly higher than average. The bump for any single condition is small.
What this means
PTPN22 regulates T-cell receptor signalling. The R620W variant is one of the most replicated non-HLA autoimmunity risk variants, contributing to risk across several seemingly unrelated conditions. Effects per condition are modest — odds ratios around 1.5–2 — but the broad influence on immune set-point is biologically interesting.
PTPN22 helps tune the signals that immune cells (T-cells) use to decide what to attack. The R620W version is one of the most consistently confirmed DNA changes — outside the HLA region — that nudges up risk for several seemingly unrelated autoimmune conditions at once. The bump for any single condition is fairly small (roughly 1.5 to 2 times the baseline odds), but the fact that one DNA change influences such a broad range of immune conditions is biologically interesting.
Caveats
- The associated risks are modest and any single condition remains uncommon.
- Most carriers never develop autoimmune disease.
- Not currently used in clinical risk stratification.
References
- Begovich et al. — A missense single-nucleotide polymorphism in a gene encoding a protein tyrosine phosphatase (PTPN22) is associated with rheumatoid arthritis (AJHG, 2004)
- Bottini & Peterson — Tyrosine phosphatase PTPN22: multifunctional regulator of immune signaling, development, and disease (Annual Review of Immunology, 2014)