Alternative Interleukin 17A/F Locus Haplotypes Are Associated With Increased Risk to Hip and Knee Osteoarthritis

Abstract

We studied the genetic epidemiology of primary large-joint (hip and knee) osteoarthritis (OA), in order to find disease risk factors by a candidate-gene approach. We used case-control study in the Croatian Caucasian population. We genotyped 500 OA patients (260 hip, 240 knee; both with total joint replacements) and 597 healthy individuals for single-nucleotide polymorphisms (SNPs) in interleukin 17A (IL17A) (rs2275913) and IL17F (rs763780 and rs1889570) genes. On the basis of our population and allelic and genotypic frequencies haplotypes were predicted by PHASE software and compared between patients and controls. The three-SNP haplotype (rs2275913-rs763780-rs1889570) G-C-A confers predisposition to hip (p < 0.005) but not knee OA. The three-SNP haplotype having opposed nucleotides A-T-G was found significantly associated with 2.6 times higher risk for developing knee (p < 0.02) but not hip OA. The haplotype G-T (IL17A-IL17F; rs2275913-rs763780) is associated with protection to the disease in hip OA (p < 0.01). Our analyses show that two disparate haplotypes within the IL17A-F gene locus are associated with higher risk to developing hip and knee OA in the Croatian population. The data might suggest a difference in the etiology of hip OA from that of the knee OA, perhaps due to an unknown dissimilarity in vulnerability of these joints to the actions of IL17. Alternatively, other differences in genetic factors like the long nonprotein coding region LINCMD1 and/or microRNA species like miR133b and miR206 found in the vicinity of the IL17 locus might be involved in the observed risk.

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

“…1). Finally, we identified six case-control studies about the association between [19], only allele model was analyzed in the overall population and Caucasian population. More characteristics of the included articles are shown in Tables 1 and 2.…”

“…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. Bai [16] and Eftedal [19] found that IL-17A/F gene polymorphisms all related to the high-risk knee OA occurrence. Bafrani [18] found that IL-17A(rs2275913) gene may be a protective factor against knee osteoarthritis while the IL-17F(rs763780) gene may be a risk factor for knee osteoarthritis.…”

“…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.…”

Common variants in IL17F gene contributed to the risk of hip osteoarthritis susceptibility in Han Chinese population

“…Most recently, a genetic epidemiology study of HOA found that the IL17A-IL17F haplotype (rs2275913-rs763780-rs1889570) G-C-A confers predisposition to HOA, and the IL17A-IL17F haplotype (rs2275913-rs763780) G-T is associated with protection from HOA in a Croatian population. 11 These results can explain a small portion of the heritability, but to date, the molecular mechanisms of HOA remain largely unknown. Furthermore, to the best of our knowledge, although 4 case-control studies have reported the relationship between the IL17F gene and knee OA with conflicting results in a Han Chinese population, there has been no study of the association of the IL17F gene with HOA in a Han Chinese population.…”

Association of NLRP3 and CARD8 Inflammasome Polymorphisms With Aseptic Loosening After Primary Total Hip Arthroplasty

“…While problems with abrasive wear of implanted hip arthroplasty materials and treatment of infections have been adequately addressed, the etiology of the non‐mechanical non‐infectious aseptic loosening of hip endoprostheses has not been established yet . The time period from implantation to aseptic loosening varies significantly between different patients with identical implants, and recent studies in this field have focused attention to possible differences in genetic host factors and polymorphisms with variability in the immune response to exogenous materials and a different response of individuals’ host tissues to external mechanical stimuli …”