The Q705K and F359L Single-Nucleotide Polymorphisms of NOD-Like Receptor Signaling Pathway: Association with Chronic Pancreatitis, Pancreatic Cancer, and Periodontitis

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Abstract

The aim of this study was to establish the correlation between the occurrence of Q705K and F359L polymorphisms in patients diagnosed with pancreatic diseases and periodontal conditions of various degrees of severity. The above-mentioned genetic markers were assessed in patients with pancreatic cancer (n = 18) and chronic pancreatitis (n = 39) as well as in a healthy control group (n = 115). The established inclusion criteria were the following: Caucasian descent, non-smoking, and age range 20–80, with different levels of periodontitis activity according to S. Offenbacher’s scale. The genotyping reactions were performed by means of an RT-PCR with the use of TaqMan® genotyping assay. Results of the study revealed that the state of periodontium was significantly worse in patients with chronic pancreatitis. The Q705K and F359L polymorphisms were associated with more advanced cases of periodontitis measured by clinical attachment level, whereas the Q705K was associated with intensified bleeding index. Furthermore, the F359L single-nucleotide polymorphism was significantly higher in the group with chronic pancreatitis (p < 0.0001; OR = 6.8571). Whereas, the prevalence of Q705K polymorphism was higher in the group of pancreatic cancer (p = 0.107; OR = 3.3939). This study suggests that the exaggerated inflammatory response provoked by Q705K and F359L might be the common denominator for periodontitis, pancreatic cancer, and chronic pancreatitis. These findings might constitute the basis for a new diagnostic and therapeutic approach.

Figures

  • Fig. 1 The inflammasome axis. The NLRP3 inflammasome is composed of NLRP3, ASC, and procaspase-1. Production of these proteins is regulated by NF-jB transcriptional factor, which in turn is stimulated by the activation of the TLR4 receptor. Please note that various factors associated with bacterial colonization act as ligands of this receptor. The interaction between the PYD and CARD domains (1 and 2) within the inflammasome leads to caspase-1 activation and cleavage of IL-1b precursor to produce an active form of IL-1b (3)
  • Table 1 Periodontal disease advancement measured by CAL, BOP, and PD mean values in association with investigated SNPs’ allele frequencies
  • Table 2 Association analysis of rs17699678 C[T polymorphism in NLRP2 with periodontitis in terms of allele and genotype distribution
  • Table 3 Association analysis of rs1769967 C[T polymorphism in NLRP2 with pancreatic diseases in terms of allele and genotype distribution
  • Table 4 Association analysis of rs35829419 C[A Q705K polymorphism in NLRP3 with periodontitis in terms of allele and genotype distribution
  • Table 5 Association analysis of rs35829419 C[A polymorphism in NLRP3 with pancreatic conditions in terms of allele and genotype distribution
  • Fig. 2 Association of the investigated genotype of NLRP2 vs. the loss of CAL
  • Fig. 3 Association of the investigated genotype of NLRP2 vs. the BOP index

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Quantitative real-time RT-PCR data analysis: Current concepts and the novel "gene expression's C <inf>T</inf> difference" formula

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APA

Miskiewicz, A., Szparecki, G., Durlik, M., Rydzewska, G., Ziobrowski, I., & Górska, R. (2015). The Q705K and F359L Single-Nucleotide Polymorphisms of NOD-Like Receptor Signaling Pathway: Association with Chronic Pancreatitis, Pancreatic Cancer, and Periodontitis. Archivum Immunologiae et Therapiae Experimentalis, 63(6), 485–494. https://doi.org/10.1007/s00005-015-0355-9

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