Bafrani Hassan Hassani, Ahmadi Monavvareh, Jahantigh Danial, Karimian Mohammad
Gametogenesis Research Center, Kashan University of Medical Sciences, Kashan, Iran.
Anatomical Science Research Center, Kashan University of Medical Sciences, Kashan, Iran.
J Cell Biochem. 2019 Oct;120(10):18020-18030. doi: 10.1002/jcb.29105. Epub 2019 May 29.
Osteoarthritis is mediated by various types of cytokines, growth factors, and inflammatory factors that the role of the interleukin-17 family in this disease is becoming increasingly apparent. The aim of this study is to determine the association between the common polymorphisms of IL17A (including rs2275913) and IL17F (including rs2397084 and rs763780) genes with the knee osteoarthritis risk which was followed by a bioinformatics approach. In a case-control study, 254 participants consisting of 127 healthy individuals and 127 subjects with knee osteoarthritis referring to Shahid Beheshti Hospital dependents on Kashan University of Medical Sciences (Kashan, Iran) were enrolled. After samples collection, the polymorphisms genotyping was determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Finally, some bioinformatics tools were used to analyze the molecular effects of the three studied polymorphisms. Data analysis showed a significant association between rs2275913-GA genotype and the decreased risk of knee osteoarthritis (OR = 0.57, 95% CI = 0.33-0.97, P = .040). However, rs763780-AG genotype (OR = 2.29, 95%CI = 1.11-4.69, P = .024) and rs763780-G allele (OR = 2.01, 95% CI = 1.09-3.72, P = .026) were associated with an increased risk of knee osteoarthritis. However, no significant associations were found between the rs2397084 polymorphism and knee osteoarthritis risk. Our structural analysis revealed that the rs2275913 polymorphism could create a new binding site for TFII-I at the promoter region of IL17A. Also, rs2397084 and rs763780 could significantly affect the function and structure of IL17A. Based on our findings, rs2275913 and rs763780 could be considered as protective and risk factors for knee osteoarthritis, respectively. Therefore, these polymorphisms can be considered as biomarkers for the screening of knee osteoarthritis susceptible persons.
骨关节炎由多种细胞因子、生长因子和炎症因子介导,白细胞介素-17家族在该疾病中的作用日益明显。本研究旨在通过生物信息学方法确定白细胞介素-17A(包括rs2275913)和白细胞介素-17F(包括rs2397084和rs763780)基因的常见多态性与膝关节骨关节炎风险之间的关联。在一项病例对照研究中,纳入了254名参与者,其中包括127名健康个体和127名膝关节骨关节炎患者,这些患者来自伊朗库姆医科大学附属沙希德·贝赫什提医院(伊朗库姆)。样本采集后,采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法确定多态性基因分型。最后,使用一些生物信息学工具分析所研究的三种多态性的分子效应。数据分析显示,rs2275913-GA基因型与膝关节骨关节炎风险降低显著相关(OR = 0.57,95% CI = 0.33 - 0.97,P = 0.040)。然而,rs763780-AG基因型(OR = 2.29,95%CI = 1.11 - 4.69,P = 0.024)和rs763780-G等位基因(OR = 2.01,95% CI = 1.09 - 3.72,P = 0.026)与膝关节骨关节炎风险增加相关。然而,未发现rs2397084多态性与膝关节骨关节炎风险之间存在显著关联。我们的结构分析表明,rs2275913多态性可在白细胞介素-17A启动子区域为TFII-I创建一个新的结合位点。此外,rs2397084和rs763780可显著影响白细胞介素-17A的功能和结构。基于我们的研究结果,rs2275913和rs763780可分别被视为膝关节骨关节炎的保护因素和风险因素。因此,这些多态性可被视为筛查膝关节骨关节炎易感人群的生物标志物。