The Influence of Polymorphisms of Interleukin-17A and -17F Genes on Susceptibility and Activity of Rheumatoid Arthritis

E, Erkol İnal; Görükmez, Özlem; Dündar, Ümit; Yener, Mahmut; Ş, Özemri Sağ; Yakut, Tahsin

doi:10.1089/gtmb.2015.0064

Cited by 12 publications

(7 citation statements)

References 19 publications

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“…Overall, 47 reports were discarded, with 14 being duplicate records and 33 having improper titles or abstracts. Among the remaining 18 studies, 1 was a scientific abstract, 20 1 was a meeting report, 21 2 were not case–control studies, 22,23 and 3 did not include key information on the IL-17A rs2275913 polymorphism. 14,24 From the remaining 11 studies, 4019 RA patients and 4137 controls were included in this meta-analysis.…”

Section: Resultsmentioning

confidence: 99%

Association between the interleukin (IL)-17A rs2275913 polymorphism and rheumatoid arthritis susceptibility: a meta-analysis and trial sequential analysis

Chen

et al. 2021

J Int Med Res

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Objective This meta-analysis was conducted to investigate the relationship between the interleukin (IL)-17A rs2275913 polymorphism and rheumatoid arthritis (RA) susceptibility. Methods Eligible studies were retrieved from PubMed, Embase, and Web of Science. The fixed- or random-effects model was used to calculate the pooled odds ratios (ORs) and 95% confidence intervals (95%CIs) on the basis of heterogeneity. Results Overall, 11 studies containing 4019 RA patients and 4137 controls were included in this meta-analysis. The results suggested a significant association between the IL-17A rs2275913 polymorphism and RA susceptibility in the overall population (allelic model A vs. G: OR = 0.89, 95%CI: 0.83–0.95; heterozygote model GA vs. GG: OR = 0.87, 95%CI: 0.78–0.96; homozygote model AA vs. GG: OR = 0.82, 95%CI: 0.71–0.96; dominant model GA + AA vs. GG: OR = 0.86, 95%CI: 0.78–0.94). In the subgroup analyses, the IL-17A rs2275913 polymorphism was significantly associated with RA risk in Europeans (allelic model A vs. G: OR = 0.87, 95%CI: 0.78–0.97; heterozygote model GA vs. GG: OR = 0.79, 95%CI: 0.68–0.93; dominant model GA + AA vs. GG: OR = 0.79, 95%CI: 0.68–0.92), but not in Africans or Americans. Conclusion This study suggests that the IL-17A rs2275913 polymorphism is significantly associated with RA susceptibility in Europeans. INPLASY registration number: INPLASY202170056.

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Section: Resultsmentioning

confidence: 99%

Association between the interleukin (IL)-17A rs2275913 polymorphism and rheumatoid arthritis susceptibility: a meta-analysis and trial sequential analysis

Chen

et al. 2021

J Int Med Res

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“…Similarly, another Polish study reported IL-17F rs763780 as risk factor of RA [ 15 ]. A group of investigators, genotyped IL-17F (rs763780, rs11465553, rs2397084) using RFLP method and established an insignificant distribution in Turkish population [ 16 ]. There were different observations even in the same population, when the literature was reviewed.…”

Section: Discussionmentioning

confidence: 99%

“…The IL-17 family of proinflammatory cytokines is made up of six distinct members: IL-17A, IL-17B, IL-17C, IL-17D, IL-17E, and IL-17F [14]. Despite the co-localization of the genes encoding IL-17A and IL-17F on the chromosome 6p12, other members of the IL-17 family are distributed across different chromosomes [15][16][17]. The expression of IL-17A and IL-17F stimulate the generation of additional cytokines, chemokines, and antimicrobial peptides, leading to the degradation of skeletal tissues and chronic inflammation in affected individuals [15].…”

Section: Introductionmentioning

confidence: 99%

Association of IL-17F rs2397084 (E126G), rs11465553 (V155I) and rs763780 (H161R) variants with rheumatoid arthritis and their effects on the stability of protein

Ali,

Kausar,

Farooq

et al. 2023

PLoS ONE

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Interleukin-17F (IL-17F), considered a pro-inflammatory cytokine, has been shown to contribute to skeletal tissue degradation and hence chronic inflammation in rheumatoid arthritis (RA). In this study we utilized bioinformatics tools to analyze the effect of three exonic SNPs (rs2397084, rs11465553, and rs763780) on the structure and function of the IL-17F gene, and evaluated their association with RA in Pakistani patients. The predicted deleterious and damaging effects of identified genetic variants were assessed through the utilization of multiple bioinformatics tools including PROVEAN, SNP&GO, SIFT, and PolyPhen2. Structural and functional effects of these variants on protein structures were evaluated through the use of additional tools such as I-Mutant, MutPred, and ConSurf. Three-dimensional (3D) models of both the wild-type and mutant proteins were constructed through the utilization of I-TASSER software, with subsequent structural comparisons between the models conducted through the use of the TM-align score. A total of 500 individuals, 250 cases and 250 controls, were genotyped through Tri-ARMS-PCR method and the resultant data was statistically analyzed using various inheritance models. Our bioinformatics analysis showed significant structural differences for wild type and mutant protein (TM-scores and RMSD values were 0.85934 and 2.34 for rs2397084 (E126G), 0.87388 and 2.49 for rs11465553 (V155I), and 0.86572 and 0.86572 for rs763780 (H161R) with decrease stability for the later. Overall, these tools enabled us to predict that these variants are crucial in causing disease phenotypes. We further tested each of these single nucleotide variants for their association with RA. Our analysis revealed a strong positive association between the genetic variant rs763780 and the risk of developing rheumatoid arthritis (RA) at both the genotypic and allelic levels. The genotypic association was statistically significant[χ2 = 111.8; P value <0.0001], as was the allelic level [OR 3.444 (2.539–4.672); P value 0.0008]. These findings suggest that the presence of this genetic variant may increase the susceptibility to RA. Similarly, we observed a significant distribution of the genetic variant rs11465553 at the genotypic level [χ2 = 25.24; P value = 0.0001]. However, this variant did not show a significant association with RA at the allelic level [OR = 1.194 (0.930–1.531); P value = 0.183]. However, the distribution of variant rs2397084 was more or less random across our sample with no significant association either at genotypic and or allelic level. Put together, our association study and in silico prediction of decreasing of IL17-F protein stabilty confirmed that two SNPs, rs11465553 and rs763780 are crucial to the suscetibility of and showed that these RA in Pakistani patients.

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“…The IL17F rs763780 C allele has been associated to an increased risk of autoimmune and inflammatory diseases such as rheumatoid arthritis in Tunisian population [32], inflammatory arthritis in a meta-analysis conducted in Caucasians [33], hip osteoarthritis in Han Chinese [34], knee osteoarthritis in Iranians [35], and psoriasis an Asians [36]. Regarding SpA, the IL17F polymorphism was associated with susceptibility to AS, disease activity and functional status in Turk patients [37], and a risk factor for SpA, AS and PsA in Brazilians [13]. According to Bafrani et al, 2019 [35] the IL17 polymorphisms can be considered biomarkers for the screening of knee osteoarthritis susceptible persons.…”

Section: Discussionmentioning

confidence: 99%

IL17F: A Possible Risk Marker for Spondyloarthritis in HLA-B*27 Negative Brazilian Patients

Neves

Visentainer

Reis

et al. 2021

JPM

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HLA-B*27 is an important marker for spondyloarthritis (SpA), however, many SpA patients are HLA-B*27 negative. Thus, the aim of this study was to investigate the influence of IL17, TNF and VDR gene polymorphisms in SpA patients who were HLA-B*27 negative. This case-control study was conducted in 158 patients [102 patients with ankylosing spondylitis (AS) and 56 with psoriatic arthritis (PsA)] and 184 controls. HLA-B*27 genotyping was performed using PCR-SSP and IL17A (rs2275913), IL17F (rs763780), TNF-308 (rs1800629), TNF-238 (rs361525), FokI C>T (rs2228570), TaqI C>T (rs731236), ApaI A>C (rs7975232), and BsmI C>T (rs1544410) using PCR-RFLP. Statistical analyses were performed by Chi-square and logistic regression using OpenEpi and SNPStats software. The IL17F C allele frequency was higher in patients with SpA, AS and PsA compared to controls. The IL17F T/C genotype frequency was higher in SpA patients in an overdominant inheritance model and when men and women were separately analyzed. IL17A_IL17F AC haplotype was significantly associated to the risk for SpA patients. As for VDR, the ApaI a/a was a potential risk factor for SpA in men. In conclusion, IL17F C variant contributed to the risk of SpA in Brazilian patients who were HLA-B*27 negative and could be a potential marker for SpA.

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The Influence of Polymorphisms of Interleukin-17A and -17F Genes on Susceptibility and Activity of Rheumatoid Arthritis

Abstract: These findings suggest that future larger scale studies with increased power should be performed to determine if the IL-17F 7488A/G and the IL-17A G197A polymorphisms are associated with the disease activity in patients with RA.

Cited by 12 publications

References 19 publications

Association between the interleukin (IL)-17A rs2275913 polymorphism and rheumatoid arthritis susceptibility: a meta-analysis and trial sequential analysis

Association between the interleukin (IL)-17A rs2275913 polymorphism and rheumatoid arthritis susceptibility: a meta-analysis and trial sequential analysis

Association of IL-17F rs2397084 (E126G), rs11465553 (V155I) and rs763780 (H161R) variants with rheumatoid arthritis and their effects on the stability of protein

IL17F: A Possible Risk Marker for Spondyloarthritis in HLA-B*27 Negative Brazilian Patients

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