Association analysis of the common varieties of IL17A and IL17F genes with the risk of knee osteoarthritis

Abstract

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.

Association of IL‐17A‐197G/A and IL‐17F‐7488T/C polymorphisms and osteoarthritis susceptibility: A meta‐analysis

“…Among the remaining 8 articles, two studies (without reporting the IL‐17A‐197G/A or IL‐17F‐7488T/C polymorphism) were excluded after full‐text assessment in the light of eligibility criteria. Ultimately, six studies went into the qualitative synthesis and meta‐analysis. The detailed process of the literature search and screening is depicted in Figure .…”

“…A total of 6 eligible studies with 1989 OA patients and 2116 healthy subjects were included in the meta‐analysis. Five studies were conducted among Asian populations and one was across a Caucasian population. All studies incorporated both female and male subjects.…”

“…Vrgoc et al’s study consisted of a knee OA cohort and a hip OA cohort in a Caucasian population. Five of the included studies were published in English and one was in Chinese. It should be noted that for IL‐17A‐197G/A , Han et al’s study was not in HWE.…”

“…Southam et al initially attempted to reveal the correlation of IL‐17A and IL‐17F gene polymorphisms and OA susceptibility in a British cohort. Afterwards, replicate studies were performed among different populations . It is quite regrettable that no convincing evidence is yet available, which might be owing to reasons such as inadequate statistical power detection caused by limited sample size, ethnicity specificity, and heterogeneity of participants.…”

Association between the polymorphism of IL-17A and IL-17F gene with knee osteoarthritis risk: a meta-analysis based on case-control studies

“…Up to now, several studies have investigated the relationships of IL-17A(rs2275913) and IL-17F(rs763780) polymorphism with knee OA risk in different countries and draw different conclusions [14][15][16][17][18][19]. Jiang [14] and Han [15] found that the IL-17A(rs2275913) polymorphism was involved in high risk of KOA while the IL-17F(rs763780) was not.…”