Promoter polymorphism (T‐1486C) of TLR‐9 gene is associated with knee osteoarthritis in a Turkish population

Abstract

In this study, we aimed to determine whether TLR-9 T-1486C SNP was associated with susceptibility to OA in the Turkish population. The study group comprised 272 patients with Grade 2-3-4 knee OA according to the Kellgren-Lawrence scoring system and the control group was formed of 296 individuals with Grade 0-1. The TLR-9 genotype were assessed by real-time polymerase chain reaction. An analysis of TLR-9 promoter -1486T/C polymorphism revealed that the -1486CC genotype appeared to have a higher risk for OA and -1486TT and -1486CT genotypes have a protective effect against the development of OA (crude OR = 0.473, 95% CI = 0.297-0.754, p = 0.002, adjusted OR = 0.531, 95% CI = 0.326-0.864, p = 0.011). This study indicate that there is a correlation of TLR-9 T-1486C gene polymorphism with advanced knee OA in a Turkish population. Changed in TLR expression due to different allelles may cause osteoarthrith development outcome cartilage degeneration. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2484-2489, 2017.

Association between TLR-9 gene rs187084 polymorphism and knee osteoarthritis in a Chinese population

“…Remarkably, rs187084 polymorphism of TLR -9 gene was located in the promoter region, and Haploview screening found it was a tagger SNP. Therefore, the association between TLR -9 gene rs187084 polymorphism and relevant diseases has been widely investigated, such as systemic lupus erythematous (SLE) [ 16 ], OA [ 12 ], malaria [ 17 ], and sepsis [ 18 ]. Recently, TLR-9 overexpression was identified in SLE patients [ 19 ], which may stimulate B cells and induce SLE pathogenesis [ 20 ].…”

“…In 2011, a two-stage case–control study with 503 OA patients and 428 controls from Taiwan revealed that the risk of OA in a Chinese population was intensified by TLR -9 gene rs187084 polymorphism and associated with T allele or TT genotype of this polymorphism [ 11 ]. Balbaloglu et al [ 12 ] replicated a positive finding in a Turkish population, but the risk of KOA was increased by the CC genotype rather than the T allele or TT genotype of rs187084 polymorphism. Regarding the conflicting findings of these studies, we conducted this hospital-based case–control study to investigate and validate the association between TLR -9 gene rs187084 polymorphism and KOA risk in a Chinese population.…”

Evaluation of the Relationship Between Common Variants in the TLR-9 Gene and Hip Osteoarthritis Susceptibility

“…Previously, all of the candidate gene association studies that have examined the relationship between TLR-9 and KOA found a significant relationship between rs187084 and the risk of KOA. Zheng et al (2017) and Balbaloglu et al (2017) both demonstrated that the CC genotype at rs187084 had a higher risk for KOA in Han Chinese individuals and Turks. However, a two-stage case-control study found that the TT genotype at rs187084 had a higher risk for KOA in a Han Chinese population from Taiwan (Su et al, 2012a).…”

“…With the rapid development of high-throughput sequencing, although more and more susceptibility variants of complex diseases have been identified (Guan et al, 2013(Guan et al, , 2014(Guan et al, , 2016a(Guan et al, , 2016b(Guan et al, , 2016cLiu et al, 2014;Zhang et al, 2018a). In recent years, researchers have identified strong association signals between the TLR-9 gene and the risk of KOA in both Han Chinese and Turkish populations (Su et al, 2012a;Balbaloglu et al, 2017;Zheng et al, 2017). For HOA, an important aspect of OA (the relationship of TLR-9 to the risk of HOA) remains largely unknown.…”

“…These results can explain a small degree of the HOA heritability; however, at present, the molecular mechanisms of HOA remain largely unknown. Recently, two candidate-gene-based genetic association studies have demonstrated that TLR-9 is associated with knee OA (KOA) in both Turkish and Chinese populations (Su et al, 2012b;Balbaloglu et al, 2017). Therefore, it is reasonable to explore whether there is an association between TLR-9 and HOA.…”