Are there specific genetic variants linked to axial spondyloarthritis?
Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that mainly affects the spine and sacroiliac joints. Genetics play a strong role in who develops the condition. The strongest known genetic link is to the HLA-B27 gene, but researchers have found many other genetic variants that increase or decrease risk. A 2026 meta-analysis of three large European studies identified several specific DNA changes associated with radiographic axSpA, some of which also affect immune system function.
What the research says
The most well-established genetic factor in axSpA is HLA-B27, which is involved in immune stress responses and is central to the disease process 1. A large 2026 meta-analysis across the UK Biobank, FinnGen, and REPAIR cohorts (2,446 radiographic axSpA cases and over 530,000 controls) found ten independent single nucleotide polymorphisms (SNPs) significantly associated with both rheumatoid arthritis and radiographic axSpA 67. Among these, risk alleles included HTTrs363075A, IKZF1rs12718261A, MANEArs72920280T, and MGAM2rs73158426G, while protective alleles were found in CARMIL1, GRM4, ITPR3, PRSS16, and ZNF322 67. The study also identified disease-specific variants: for example, the BTN2A1rs1977199A allele was protective in rheumatoid arthritis but increased risk for radiographic axSpA (odds ratio 1.23) and was linked to reduced IL-22 levels 67. Other variants in BTN3A2 and H2BC11 showed opposite effects between the two diseases 67. These genetic variants often act as expression quantitative trait loci (eQTLs), meaning they influence the activity of nearby immune-related genes, which helps explain how they might contribute to inflammation in axSpA 67.
What to ask your doctor
- Should I consider genetic testing for HLA-B27 or other variants to help confirm my diagnosis?
- How do my genetic results affect my treatment options or prognosis?
- Are there any family members who should be screened for axSpA given the genetic links?
- What do the newer genetic variants (like BTN2A1 or IKZF1) mean for my disease risk or progression?
- Can genetic information help predict how I might respond to biologic therapies?
This question is drawn from common patient questions about Rheumatology and answered using cited medical research. We do not provide individualized advice.