Involvement of polymorphisms of TNF, CRP and SAA1 genes in the predisposition to the development of ankylosing spondylitis and its clinical manifestations

• Published in: Nauchno-prakticheskai͡a︡ revmatologii͡a Vol. 60; no. 1; pp. 64 - 71
• Main Authors: Krylov, M. Yu, Guseva, I. A., Sakharova, K. V., Samarkina, E. Yu, Erdes, S. F., Konovalova, N. V., Varlamov, D. A.
• Format: Journal Article
• Language: English; Russian
• Published: IMA PRESS LLC 01.03.2022
• Subjects: ankylosing spondylitis; crp gene; enthesitis; peripheral arthritis; polymorphism; saa1 gene; tnf-α gene
• ISSN: 1995-4484; 1995-4492
• DOI: 10.47360/1995-4484-2022-64-71

Objective. To study the involvement of the rs1800629 G/A polymorphisms of the TNF-α gene, rs1205C/T of the CRP gene, and rs12218T/C of the SAA1 gene in the predisposition to ankylosing spondylitis (AS) and their role in the formation of clinical phenotypes of AS. Materials and methods. 122 patients with AS were included in the study. All patients had a diagnosis of AS based on the modified New York criteria. The presence of the HLA-B27 antigen was detected in 109 (89.3%) patients, the presence of peripheral arthritis – in 71 (58.2%), enthesitis – in 92 (75.4%), coxitis – in 82 (67.2%) patients. All patients had a high degree of activity with an average BASDAI index of 5.6±1.2. The control group consisted of 142 healthy blood donors. Polymorphisms were studied using allele-specific real-time polymerase chain reaction (RT-PCR). Results. Significant differences were found in the frequencies of genotypes and alleles of the -308G/A polymorphism of the TNF gene and the frequencies of alleles of the rs12218 T/C polymorphism of the SAA1 gene between patients and the control group (p=0.01, p=0.01 and p=0.03 respectively). Logistic regression analysis showed that the presence of at least one -308A allele in the patient’s genotype reduced the risk of developing AS by 4.4 times compared with the GG genotype (p=0.006). In carriers of the GA genotype, the probability of a predisposition to the development of enthesitis was 2.2 times lower than in carriers of the GG genotype (p=0.01). The relationship between the rs1205 polymorphism of the CRP gene and the predisposition to peripheral arthritis has been established. Carriage of the rs1205T allele doubled the susceptibility to arthritis compared with the rs1205C allele (p=0.013). Carriage of at least one rs12218C allele of the SAA1 gene doubled the susceptibility to AS (p=0.018). Conclusion. The data obtained confirm the involvement of polymorphisms rs1800629 of the TNF gene, rs1205 of the CRP gene, and rs12218 of the SAA1 gene in the predisposition to AS. TNF gene polymorphism is associated with the formation of the clinical phenotype of enthesitis, and CRP gene polymorphism is associated with a predisposition to peripheral arthritis.