Single Nucleotide Polymorphisms within the microRNA Binding Site of SET8 Modify Ankylosing Spondylitis Risk

Objectives: Genetic polymorphisms in microRNA binding sites (mir-SNPs) may affect rheumatic diseases risk. We genotyped two mir-SNPs in the 3' UTR of SET8 (rs16917496) and KRT81 (rs3660) in ankylosing spondylitis (AS) patients to assess their association with AS risk. Methods: DNAs were extracted from blood samples for polymerase chain reaction analysis. Western blot was used to detect protein expression. Plasma reactive oxygen species (ROS) levels were measured by fluorescent probe technology. Results: We found that SET8 CC genotype had an increased chance of developing AS than the TT + CT genotype carrier (odds ratio, 5.378; 95% confidence interval, 1.130-25.593; p = 0.019). Moreover, the SET8 CC genotype displayed a lower expression of SET8 than the TT genotype. Additionally, increased ROS generation in AS patients was observed compared with controls (23859.055 ± 12283.038 vs. 14758.330 ± 5854.946, p < 0.001). Furthermore, the AS-susceptible CC genotype was associated with high ROS levels (35062.000 ± 17748.785 vs. 22629.463 ± 11002.181, p = 0.033). Conclusion: Our study revealed that the SNP rs16917496 located in the miR-502 binding site in the 3' UTR of SET8 could be used as a biomarker to predict AS risk. Importantly, SNP rs16917496 could participate in the pathogenesis of AS by regulating the expression of SET8, thereby promoting oxidative stress levels.