Abstract
BackgroundInterleukin-17 (IL-17), a pleiotropic cytokine, plays a significant role in the inflammatory diseases. By a pilot study with small population, IL-17 polymorphisms (IL-17A rs2275913 and IL-17F rs763780) showed a more potential risk factor in knee osteoarthritis (OA) in our recruited subjects. In the current study, the association between IL-17A rs2275913 and IL-17F rs763780and the risk of OA in a Chinese population is studied.MethodsThe IL-17A rs2275913 and IL-17F rs763780 polymorphisms were determined in 594 knee OA cases and 576 healthy controls, using polymerase chain reaction-restriction fragment length polymorphism assay. The relationship between genotype distribution and disease risk, as well as OA severity was analyzed by Chi-square test and multivariate logistic regression.ResultsThe experimental results indicated that the polymorphism in IL-17 gene rs2275913 site were related to knee OA risk after the adjustment of BMI, sex, age, smoking and drinking status (AA vs. GG: odds ratio (OR), 1.411; 95% confidence interval (CI), 1.021–1.950; P = 0.040; A allele vs. G allele: OR, 1.192; P = 0.037; 95% CI, 1.012–1.404;). Similarly, subjects who are bearing the rs763780 variant genotypes (TC and CC) and C allele also had a higher susceptibility to knee OA compared with those who are bearing the TT genotype (TC vs. TT, OR: 1.312; P = 0.039; 95% CI: 1.017–1.692; CC vs. TT, OR: 2.812, P = 0.006, 95% CI: 1.338–5.909; C allele Vs. T allele, OR:1.413, P = 0.002, 95% CI:1.141–1.751). In the meantime, one high-risk haplotypes, AC (OR was 7.22, P < 0.01) was found. Both two polymorphisms do not correlated with OA severity based on Kellgren-Lawrence (K&L) scales. Finally, serum IL-17 levels of knee OA patients were greatly higher than those of controls (P = 0.001).ConclusionsWith the limited size sample, our study shows that IL-17 gene polymorphisms possibly related to the high-risk knee OA occurrence.
Highlights
Interleukin-17 (IL-17), a pleiotropic cytokine, plays a significant role in the inflammatory diseases
Dominant and recessive model demonstrated the similar results that A allele of rs2275913 and C allele of rs763780 increase the risk of knee OA
Previous studies implicated that IL-17/IL23 pathway and TH17 cells play an important role in inflammation-related diseases [28], and several meta-analysis examined the relationship between IL-17A and IL-17F gene polymorphisms and the risk of inflammatory diseases, including periodontitis, rheumatoid arthritis (RA), and inflammatory bowel disease, and all these documents demonstrate that IL-17 polymorphisms may increased the RA risk, but dependent with race and ethnic groups [29]
Summary
Interleukin-17 (IL-17), a pleiotropic cytokine, plays a significant role in the inflammatory diseases. By a pilot study with small population, IL-17 polymorphisms (IL-17A rs2275913 and IL-17F rs763780) showed a more potential risk factor in knee osteoarthritis (OA) in our recruited subjects. Bai et al BMC Medical Genetics (2019) 20:20 immune cell infiltration and cytokine secretion [12]. Both Innate immune system activation [13] and T-cell mediated inflammatory pathway play central roles in disease development and progression [14]. Previous studies demonstrate that IL-17 is expressed in synovial tissues, and could contribute to cartilage breakdown and synovial infiltration in OA by inducing the release of chemokines by chondrocytes [19] and augments nitric oxide production in OA cartilage via nuclear factor kappa B activation [20]
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