Association of Toll-Like Receptor 5 Gene Polymorphism with Susceptibility to Ossification of the Posterior Longitudinal Ligament of the Spine in Korean Population

Department of Oriental Rehabilitation Medicine, College of Oriental Medicine, Kyung Hee University, Seoul, Korea.
Journal of Korean Neurosurgical Society (Impact Factor: 0.64). 01/2011; 49(1):8-12. DOI: 10.3340/jkns.2011.49.1.8
Source: PubMed


Ossification of the posterior longitudinal ligament (OPLL) has a strong genetic component. Specific gene polymorphisms may be associated with OPLL in several genes which regulate calcification in chondrocytes, change of extracellular collagen matrix and secretions of many growth factors and cytokines controlling bone morphogenesis. Toll-like receptor 5 (TLR5) may play a role in the pathogenesis of OPLL by intermediate nuclear factor-kappa B (NF-κB). The current study focused on coding single nucleotide polymorphisms (SNPs) of TLR5 for a case-control study investigating the relationship between TLR5 and OPLL in a Korean population.
A total of 166 patients with OPLL and 231 controls were recruited for a case-control association study investigating the relationship between SNPs of TLR5 gene and OPLL. Four SNPs were genotyped by direct sequencing (rs5744168, rs5744169, rs2072493, and rs5744174). SNP data were analyzed using the SNPStats, SNPAnalyzer, Haploview, and Helixtree programs. Multiple logistic regression analysis with adjustment for age and gender was performed to calculate an odds ratio (OR).
None of SNPs were associated with OPLL in three alternative models (codominant, dominant, and recessive models; p > 0.05). A strong linkage disequilibrium block, including all 4 SNPs, was constructed using the Gabriel method. No haplotype was significantly associated with OPLL in three alternative models.
These results suggest that Toll-like receptor 5 gene may not be associated with ossification of the posterior longitudinal ligament risk in Korean population.

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    • "Several groups worked on candidate gene association studies. A number of genes/loci associated with the OPLL susceptibility have been reported, including genes for nucleotide pyrophosphatase/phosphodiesterases (NPPS)/ENNP1[18], transforming growth factor (TGF)-β1[19], estrogen receptor (ESR),[20] interleukin 1, beta (IL-1β),[20] vitamin D receptor (VDR),[21] bone morphogenetic protein 2 (BMP2),[22] runt-related transcription factor 2 (RUNX2),[23] toll-like receptor 5 (TLR5),[24] interleukin 15 receptor, alpha (IL-15RA),[25] and BMP9 [26] (Table 1). However, the results of these studies are not sufficiently convincing because of their small sample sizes, small number of sequence variants examined and lack of functional proof of the variants and/or genes. "
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    ABSTRACT: Ossification of the posterior longitudinal ligament of the spine (OPLL) is a common disease in aging populations and sometimes results in serious neurological problems due to compression of the spinal cord and nerve roots. OPLL is a multi-factorial (polygenic) disease controlled by genetic and environmental factors. Studies searching for the genetic component of OPLL, using linkage and association analyses, are in progress and several susceptibility genes have been reported. This paper reviews the recent progress in the genetic study of OPLL and comments on its future task.
    Full-text · Article · May 2014
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    • "The intracellular region includes a signaling portion, the Toll/IL-1 receptor (TIR) domain, which binds adaptor molecules and induces cellular immune responses through a signaling cascade (Muzio et al., 2000). TLR5 polymorphisms play a role in various complex human diseases, including Legionnaire's disease (Hawn et al., 2003), Crohn's disease (Gewirtz et al., 2006), ossification of the posterior longitudinal ligament of the spine (Chung et al., 2011), systemic lupus erythematosus (Hawn et al., 2005), and recurrent cystitis (Hawn et al., 2009). In German shepherd dogs, the non-synonymous single nucleotide polymorphisms (SNPs) c.22GA (p.Ala8Thr), c.100C > T (p.Arg34Cys) and c.1844T > C (p.Leu615Ser) have been associated significantly with inflammatory bowel disease (Kathrani et al., 2010). "
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    ABSTRACT: The Toll-like receptor 5 (TLR5) recognizes flagellin of Gram-positive and -negative bacteria and plays an important role in the host defense system. Here, we surveyed single nucleotide polymorphisms (SNPs) in the coding sequence of the porcine TLR5 gene in 83 individuals from five pig breeds, these including Chinese local populations and Western commercial pig breeds. A total of 19 medium polymorphic SNPs (0.25 < PIC < 0.5) were identified, three of which were missense mutations that clustered within the extracellular domain of TLR5. One of the non-synonymous SNPs fell within a 228-amino acid region which has been shown to be important for flagellin recognition. Four SNPs were only found with high frequencies in Oriental pig breeds. The 19 SNPs were found in 30 haplotypes, one of which segregated at high frequency in all samples. Compared with Western pig breeds, Chinese local populations had higher genetic diversity and more haplotypes. Tajima's test showed no evidence for deviation from neutrality. The data provide useful information for future genetic marker characterization by means of disease association analysis and/or stimulating the mutation carrier with relevant ligands.
    Preview · Article · Mar 2013 · Genetics and Molecular Biology
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    • "A variety of possible risk factors have been implicated in OPLL using epidemiological studies; these factors include sex, trauma, hormonal imbalance, dietary habits, and lifestyle factors (e.g., diabetes mellitus)7). Genetic and environmental factors interact in OPLL and the genetic background is considered as a predominant factor in the etiology of OPLL1,5,12,16). Recent molecular genetic studies identified several candidate genes for susceptibility to this disease. These genes included collagen 11A2, BMP-4, nucleotide pyrophosphatase, TGF-β1, TGF-β3, ESR1, IL-1B, and retinoic X receptor; however, none of these genes have been confirmed as being pathogenetically relevant for OPLL patients7,16). "
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    ABSTRACT: The aim of this study was to determine whether single nucleotide polymorphisms (SNPs) of fibroblast growth factor (FGF) 2 gene and fibroblast growth factor receptor (FGFR) genes are associated with ossification of the posterior longitudinal ligament (OPLL). A total of 157 patients with OPLL and 222 controls were recruited for a case control association study investigating the relationship between SNPs of FGF2, FGFR1, FGFR2 and OPLL. To identify the association among polymorphisms of FGF2 gene, FGFR1, FGFR2 genes and OPLL, the authors genotyped 9 SNPs of the genes (FGF2 : rs1476217, rs308395, rs308397, and rs3747676; FGFR1 : rs13317 and rs2467531; FGFR2 : rs755793, rs1047100, and rs3135831) using direct sequencing method. SNPs data were analyzed using the SNPStats, SNPAnalyzer, Haploview, and Helixtree programs. Of the SNPs, a SNP (rs13317) in FGFR1 was significantly associated with the susceptibility of OPLL in the codominant (odds ratio=1.35, 95% confidence interval=1.01-1.81, p=0.048) and recessive model (odds ratio=2.00, 95% confidence interval=1.11-3.59, p=0.020). The analysis adjusted for associated condition showed that the SNP of rs1476217 (p=0.03), rs3747676 (p=0.01) polymorphisms in the FGF2 were associated with diffuse idiopathic skeletal hyperostosis (DISH) and rs1476217 (p=0.01) in the FGF2 was associated with ossification of the ligament flavum (OLF). The results of the present study revealed that an FGFR1 SNP was significantly associated with OPLL and that a SNP in FGF2 was associated with conditions that were comorbid with OPLL (DISH and OLF).
    Full-text · Article · Jul 2012 · Journal of Korean Neurosurgical Society
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