Ankylosing spondylitis (AS) is a potentially disabling form of a systemic chronic inflammatory arthritis affecting mainly the axial skeleton, with or without extraspinal manifestations. The genetic basis of AS is partly known. Moreover, many autoimmunityrelated genes have pleiotropic effects. Multiple functional polymorphisms in the genes encoding the tumor necrosis factor (TNF) superfamily of cytokines, their receptors, and signaling proteins, are associated with susceptibility to autoimmune diseases. These arguments prompted us to conduct a study evaluating a possible association of single nucleotide polymorphism (SNP) rs4810485 of the CD40 gene, found previously to be involved in other inflammatory diseases, with susceptibility to AS in the Latvian population; 98 AS patients from the Center of Rheumatology of Pauls Stradins Clinical University Hospital were selected as the case group and 154 ethnically related healthy subjects from the Genome Database of the Latvian Population were included as a control group. CD40 gene rs4810485 polymorphism was tested by a TaqMan Pre- Designed SNP Genotyping Assay. In the case of CD40 gene rs4810485 polymorphism, the minor allele is T. Compared to the control subjects, the case group had a higher frequency of the minor allele T (28.6% vs. 17.5%; p=0.00345).The T allele was the risk allele for disease onset (OR 1.88 (95% CI 1.23-2.88)). The relationship between the disease and genotypes was of moderate significance (V=0.20). As for genotypes, GT and TT were the susceptibility genotypes for AS (respectively OR 2.42 (95% CI 1.38 – 4.25) and 1.94 (95% CI 0.71-5.32)). The GG genotype had a protective feature (OR 0.43 (95% CI 0.25 – 0.73)). A significant difference was not found in the analysis of the SNP alleles and genotype distribution in the peripheral arthritis (p=0.85 and p=0.86, respectively) and uveitis (p=0.47 and p=0.3, respectively) subgroups of AS patients. The study data showed that CD40 gene rs4810485 polymorphism is associated with risk of AS.