The Genetic Background of Ankylosing Spondylitis Reveals a Distinct Overlap with Autoimmune Diseases: A Systematic Review.

: Ankylosing Spondylitis (AS) is a rare autoinflammatory disorder affecting 0.1-1.4% of the population, with increasing recognition over the past 20 years. Although the specific causes of AS remain unclear, the presence of the gene is associated with increased risk, though only 1-5% of carriers develop the disease. Despite extensive research, no definitive lab tests exist, and many patients are diagnosed years after symptom onset. : In the present study, in order to investigate the disease's genetic background in correlation with autoimmune diseases, a metanalysis has been performed following PRISMA guidelines using Scopus and PubMed publications towards extracting single-nucleotide polymorphisms (SNPs) of high importance for the disease. Moreover, the polymorphisms have been annotated and analyzed using information from several databases, including PubMed, LitVar2, ClinVar, and Gene Ontology. : From 1940 screened titles and abstracts, 57,909 studies were selected, with 539 meeting the inclusion criteria. The genetic background of AS is described through 794 genetic variants, of which 76 SNPs are directly associated with AS (Classes A and B), predominantly located in intronic regions. and emerged as key genes implicated in AS, while chromosomes 1, 2, and 5 accumulated the most associated SNPs. Functional enrichment revealed strong associations with immune regulation and interleukin signaling pathways, particularly and signaling. promotes inflammation in AS, while tries to suppress it, acting as an anti-inflammatory cytokine. Of the 78 AS-related SNPs, 16 were unique to AS, while 66 were common to autoimmune diseases, especially rheumatoid arthritis (RA) and psoriasis (PsO), suggesting genetic overlap between these diseases. : This study creates a comprehensive genetic map of AS-associated SNPs, highlighting key pathways and genetic overlap with autoimmune diseases. These findings contribute to understanding disease mechanisms and could guide therapeutic interventions, advancing precision medicine in AS management.