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

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.

Polymorphism of nucleotide binding domain-like receptor protein 3 (NLRP3) increases susceptibility of total urinary arsenic to renal cell carcinoma

“…One study found that the NLRP3 rs35829419 C > A (Q705K) genotype was associated with a lower survival rate in patients diagnosed with invasive colorectal cancer 49 . However, this genotype was not associated with myeloid leukemia 50 or pancreatic cancer 51 . However, the NLRP3 alleles of rs10925025 G, rs1539019 C, rs10925026 A, and rs12143966 A tended to correlate with the risk of RCC in this study.…”

Gene expression profiling reveals U1 snRNA regulates cancer gene expression

“…Among these 12 pathways, three well-known cancer pathways were p53 signaling pathway (KEGG: rno04115), bladder cancer (KEGG: rno05219) and pathways in cancer (KEGG: rno05200). As for the other nine pathways, MAPK signaling pathway (KEGG: rno04010) [8], cell cycle pathway (KEGG: rno04110) [9], cytokine-cytokine receptor interaction pathway (KEGG: rno04060) [10], NOD-like receptor signaling pathway (KEGG: rno04621) [11], cytosolic DNA-sensing pathway (KEGG: rno04623) [12], RIG-I-like receptor signaling pathway (KEGG: rno04622) [13], Toll-like receptor signaling pathway (KEGG: rno04620) [14], chronic myeloid leukemia pathway (KEGG: rno05220) [15] and Hematopoietic cell lineage pathway (KEGG: rno04640) [16] were also reported to be associated to cancers in the previous studies. To confirm the results from the microarray data analysis, the expression levels of six out of the total 21 DE genes ( Figure 2 ) in pathways in cancer (KEGG: rno05200) were measured using the qPCR.…”

Gene expression profiling reveals U1 snRNA regulates cancer gene expression

“…Among these 12 pathways (Table 1 ), three well-known cancer pathways were p53 signaling pathway (KEGG: rno04115), bladder cancer (KEGG: rno05219) and pathways in cancer (KEGG: rno05200). As for the other nine pathways, MAPK signaling pathway (KEGG: rno04010) [ 9 ], cell cycle pathway (KEGG: rno04110) [ 10 ], cytokine-cytokine receptor interaction pathway (KEGG: rno04060) [ 11 ], NOD-like receptor signaling pathway (KEGG: rno04621) [ 12 ], cytosolic DNA-sensing pathway (KEGG: rno04623) [ 13 ], RIG-I-like receptor signaling pathway (KEGG: rno04622) [ 14 ], Toll-like receptor signaling pathway (KEGG: rno04620) [ 15 ], chronic myeloid leukemia pathway (KEGG: rno05220) [ 16 ] and Hematopoietic cell lineage pathway (KEGG: rno04640) [ 17 ] had also been associated to cancers in previous studies. Among the total 73 genes involved in 12 enriched pathways, 56 and 17 were up- and down-regulated, respectively ( Supplementary Table 3 ).…”