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

Abstract

Objective: Hip osteoarthritis (HOA) is one of the most common types of osteoarthritis and affects nearly 10% of men and 18% of women who are >60 years of age worldwide. It has been demonstrated to be a genetic disease with a 50% heritability risk. Recently, the TLR-9 gene has been associated with knee OA in both Turkish and Chinese populations, but the relationship between the TLR-9 gene and HOA has not been evaluated. In this study, we aimed to evaluate the relationship between the common genetic variants in the TLR-9 gene and the predisposition of Han Chinese individuals to HOA. Methods: A total of 730 HOA patients and 1220 healthy controls were recruited in a hospital-based case-control study. Six common single nucleotide polymorphisms (SNPs) of the TLR-9 gene were selected for genotyping, and genetic association analyses were performed using both single-marker and haplotype-based methods. Results: The SNP rs187084 was found to be significantly associated with the risk of HOA after a Bonferroni correction (adjusted allelic p-values with age, gender, and body mass index [BMI] = 0.0008). The results indicated that the A allele of rs187084 is a risk allele for HOA and is likely to be a predisposing factor leading to an increased risk of HOA (adjusted odds ratio with age, gender, and BMI = 1.26, 95% confidence interval = 1.10-1.43). The results of the haplotype analyses confirmed a similar pattern to the SNP analyses. Conclusions: Our study provides strong evidence that variations in the TLR-9 gene are closely linked with genetic susceptibility to HOA in the Han Chinese population. This finding furthers the role of TLR-9 in the development and occurrence of OA in general.

Potential Impact of Polymorphisms in Toll-like Receptors 2, 3, 4, 7, 9, miR-146a, miR-155, and miR-196a Genes on Osteoarthritis Susceptibility

“…Although our study did not show an association with OA risk, several studies have found a positive association between TLR9 SNP rs187084 and susceptibility to OA [ 31 , 32 , 33 ]. Previous studies reported the T allele of rs187084 as associated with advanced stages of knee OA [ 31 ] and hip OA [ 18 ], while another study reported the C allele as a risk factor for knee OA [ 33 ].…”

“…Cartilage deterioration in OA joints may be a consequence of TLR-ligand interactions with robust proinflammatory signaling [ 18 ]. TLR1, TLR2, TLR4, and TLR9 expression has been reported to be upregulated in OA chondrocytes [ 34 ], whereas TLR1-7 and TLR9 are upregulated in OA synovium [ 3 ].…”

“…The polymorphism rs3853839 (C/G) located in the 3′ untranslated region (UTR) of the TLR7 gene is associated with upregulated mRNA expression and increased SLE risk [ 16 ], and, recently, with knee osteoarthritis susceptibility [ 17 ]. Polymorphism rs187084 (A/G), located in the promoter of the TLR9 gene, alters TLR9 expression and previously was associated with hip OA risk [ 18 ]. Two of the most-studied polymorphisms in miRNA genes, miR-146a rs2910164 (C/G) and miR-155 rs767649 (A/T), located in the regulatory regions, have been associated with SLE risk [ 19 ].…”

NFKB2 polymorphisms associate with the risk of developing rheumatoid arthritis and response to TNF inhibitors: Results from the REPAIR consortium

“…Associated with psoriatic arthritis risk 69 , hip and knee osteoarthritis 70,71 , SLE 72 and IBD 73 ; associated with the risk of autoimmune thyroid disease 74 ; response to anti-TNF therapy in patients with RA 64 34 and DNA samples were obtained from peripheral blood collected at the Statens Serum Institut (Copenhagen, Denmark), which routinely perform screening for tuberculosis before treatment with biological treatments. Healthy blood donors were recruited in Viborg and Sønderborg (Denmark).…”

An insight into osteoarthritis susceptibility: Integration of immunological and genetic background

“…Several studies reported rs187084 (-1486, T>C) polymorphism of the TLR9 gene as a predisposing genetic marker for knee OA development in Chinese [53,54] and Turkish population [55]. The polymorphism rs187084 was also found to be significantly associated with hip OA risk [56].…”