Association of a functional polymorphism in the promoter region of TLR‐3 with osteoarthritis: A two‐stage case–control study

Abstract

Recent studies have suggested that polymorphisms in toll-like receptor 9 (TLR-9), an endosomal TLR, are associated with knee osteoarthritis (OA). TLR-3, -7, and -8 are also found on the surface of endosomes and to investigate whether similar associations exist with polymorphisms in these TLR genes we performed a two-stage case-control study and genotyped 11 TLR single nucleotide polymorphisms (SNPs) in 823 OA cases and 594 healthy controls by polymerase chain reaction restriction fragment length polymorphism assays. Real-time PCR was performed to assess the functional expression of an identified promoter polymorphism in TLR-3 following dexamethasone stimulation of articular chondrocytes. An association between TLR-3 SNPs at rs3775296 and rs3775290 and OA was identified in both populations. In males the allelic frequencies of TLR-7 rs179010 and TLR-8 rs5744080 were significantly different between OA cases and healthy controls. The ATCA, CTCA, and CCTA haplotypes of TLR-3 were associated with OA susceptibility. A significant difference in TLR-3 gene expression following dexamethasone treatment was seen among the various genotypes of rs3775296 (p ¼ 0.004). Our findings indicate that a SNP in the promoter region of TLR-3 is associated with elevated TLR-3 gene expression and susceptibility to knee OA in a Chinese Han population.

Role of Toll-Like Receptor 3 Gene Polymorphisms in Preeclampsia

“…However, contrasting results were also observed. Hsin-Yi et al observed that the rs3775291 has no significant genotype and allele association between osteoarthritis cases and healthy controls in a Chinese Han population [31]. In this study, we did not find an association in the genotype and allele frequencies of rs3775291 between PE patients and healthy pregnant women.…”

“…In this study, we did not find an association in the genotype and allele frequencies of rs3775291 between PE patients and healthy pregnant women. Hsin-Yi et al have shown that rs3775296, located in the 5′-UTR of TLR3, is associated with elevated TLR3 expression and susceptibility to knee osteoarthritis in a Chinese Han population [31]. Moreover, the rs3775296-T allele was associated with photosensitivity and anemia of system lupus erythematosus in females in a Taiwanese population [32].…”

Association of Toll-Like Receptor 3 and Toll-Like Receptor 9 Single Nucleotide Polymorphisms with Hepatitis C Virus Infection and Hepatic Fibrosis in Egyptian Patients

“…21 It has been suggested that promoter polymorphisms in TLR-3 (c.1377C/T, _7 C/A) influence gene expression in response to inflammatory cytokines and causes transcriptional modulation in TLR-3. 22 Human TLR-3 promoter region contains a functional IFN-stimulated response element/IRF element. 23 TLR-9 1237T/C SNP confers regulatory effects on TLR-9 transcription; higher transcriptional activity was seen in the presence of the CC allelic variant with moderate increase in promoter activity.…”

A Functional Polymorphism in the Promoter Region of TLR3 Is Associated with Susceptibility to End-Stage Renal Disease

“…A number of studies have revealed that some SNPs in TLR3 are associated with several human diseases, such as OA [10], nasopharyngeal carcinoma [26] and systemic lupus erythematosus (SLE) [27]. Here, the -7C/A polymorphism of TLR3 was strongly associated with ESRD.…”

“…Single-nucleotide polymorphisms (SNPs) in TLR3 have been correlated with diseases such as osteoarthritis (OA) [10], type 1 diabetes mellitus (T1DM) [11], asthma [12] and bladder cancer [13]. Previous studies have indicated that the presence of TLR3 SNPs influences promoter activity (gene expression), mRNA conformation (stability) and subcellular localisation of mRNAs and/or protein structure and function.…”