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Potential role of Toll-like receptor 2 expression and polymorphisms in colon cancer susceptibility in the Saudi Arabian population.

ABSTRACT: Background:Inflammation is a fundamental factor that contributes to the development and progression of several types of cancer including colon cancer. Toll-like receptors (TLRs) and their signaling pathways have been reported to be associated with chronic inflammation and thereby induced cancer. Our aim was to investigate the expression and polymorphisms of TLR2 and their association with colon cancer. Methods:Real-time PCR and immunohistochemistry were used to investigate TLR2 gene expression and to evaluate the potential risk of predisposition to colon cancer caused by three tagging single-nucleotide polymorphisms (SNPs) on TLR2, including rs3804100, rs4696480, and rs3804099. TaqMan assay was conducted on samples from 115 patients with colon cancer and 102 age- and sex-matched normal individuals. Results:We found that, TLR2 was highly expressed in epithelial colon cancer cells and both TLR2 mRNA and protein levels, and significantly decreased in tumor tissues compared to normal tissues. Two of three TLR2 SNPs increased the risk of colon cancer. However, TLR2 rs3804099 increased the risk of colon cancer development by more than 3.8- and 5-fold in female patients and patients aged less than 57 years, respectively. The T allele of TLR2 rs3804100 showed a significant association with patients less than 57 years. In silico analysis of the TLR2 nucleotide substitution in SNP rs3804100 and rs3804099 determined that 67% and 70% probability of these single nucleotide variants alter splicing phenotypes, rs3804100 more specifically result on activating an additional splice site. Genotype and allele frequencies of rs4696480 were similar between the overall study populations. Thus, TLR2 rs4696480 appear to be not involved in colon cancer in our study population. Conclusions:There was a significant link between innate immunity deregulation through disruption of the TLRs and potential development of colon cancer. These SNPs can be used as screening markers for predicting colon cancer risk earlier in life to implement necessary prevention.

SUBMITTER: Semlali A

PROVIDER: S-EPMC6241690 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Potential role of Toll-like receptor 2 expression and polymorphisms in colon cancer susceptibility in the Saudi Arabian population.

Semlali Abdelhabib A Parine Narasimha Reddy NR Al-Numair Nouf S NS Almutairi Mikhlid M Hawsawi Yousef M YM Amri Abdullah Al AA Aljebreen Abdulrahman M AM Arafah Maha M Almadi Majid A MA Azzam Nahla Ali NA Alharbi Othman O Alanazi Mohammad Saud MS

OncoTargets and therapy 20181114

<h4>Background</h4>Inflammation is a fundamental factor that contributes to the development and progression of several types of cancer including colon cancer. Toll-like receptors (<i>TLRs</i>) and their signaling pathways have been reported to be associated with chronic inflammation and thereby induced cancer. Our aim was to investigate the expression and polymorphisms of <i>TLR2</i> and their association with colon cancer.<h4>Methods</h4>Real-time PCR and immunohistochemistry were used to inves ...[more]

PMID: 30532554

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Project description:Diabetes mellitus is a complex disease with a wide range of manifestations. Diabetes, notably type 2 diabetes mellitus (T2DM), is becoming more common in Saudi Arabia as a result of obesity and an aging population. T2DM is classified as a noncommunicable disease, and its incidence in the Saudi population continues to grow as a consequence of socioeconomic changes. Toll-like receptors (TLRs) are innate immune receptors that mediate the inflammatory response in diabetes mellitus. Previous studies have documented the relationship between different SNPs in the TLR9 gene in different forms of diabetes. As a result, the purpose of this study was to investigate the relationship between rs187084, rs352140, and rs5743836 SNPs in the TLR9 gene among T2DM patients in the Saudi population. This was a case-control study that included 100 T2DM cases and 100 control subjects. The three SNPs were identified in the study population (n = 200) using polymerase chain reaction (PCR), restriction enzymes for rs352140, and Sanger sequencing for rs187084 and rs5783836. Next, statistical analyses were performed using various software to determine the association between the SNPs and T2DM. rs187084 and rs5743836 were associated with an increased risk of T2DM development. rs187084 and rs5743836 allelic frequencies were associated with a 3.2 times increased risk of T2DM development (p < 0.05). DBP was associated with T2DM (p = 0.02). rs187084 was associated with TC and HDLc; rs352140 was associated with DBP, HbA1c, and HDLc; rs5743836 was associated with waist (p < 0.05). The CGT haplotype was strongly associated with T2DM (p < 0.003). Gene-gene interaction, graphical presentation, and dendrogram showed the strong association with T2DM patients (p < 0.05). This study concluded that rs187084 and rs5743836 were strongly associated with T2DM in Saudi Arabian patients. This study provides further evidence that SNPs in the TLR9 gene play a significant role in T2DM development in a Saudi community.

Project description:BACKGROUND:The IL-4 receptor alpha subunit (IL-4R?), when associated with the common gamma chain receptor, or the IL-13R?1 subunit, transduces signals to STAT6 in response to IL-4 and IL-13 stimulations. This results in a number of cell-specific responses including Th2 differentiation, lymphocyte proliferation and IgE production. Given the prominent role of IL-4R? in allergic disorders, several single-nucleotide polymorphisms (SNPs) have been found associated with asthma and other atopic disorders, including rs1805010 (I75V) and rs1801275 (Q576R) SNPs; however, lack of significant association have also been reported for some ethnic groups. The objective of this study was to determine whether IL-4R? rs1805010 and rs1801275 polymorphisms are associated with asthma in patients from Saudi Arabia. MATERIALS AND METHODS:One hundred and ninety severe asthmatic patients (11-70 years old) and 194 healthy subjects of equivalent age range were recruited for blood donation. DNA was purified and genotyping for rs1801275 and rs1805010 polymorphisms in the IL-4R? gene was performed by PCR amplification, followed by cycle sequencing of the purified PCR fragments using BigDye chain terminator and capillary electrophoresis. RESULTS:Pearson's Chi-square tests showed that the minor alleles, G, for both rs1805010 and rs1801275 SNPs, were significantly more frequent in asthmatics than in the healthy group (Yates' P < 0.05); conversely, the major alleles, A, were significantly more frequent in healthy than in asthmatics (P < 0.05). Concerning association analysis, odds for A/G-G/G genotypes were significantly higher to be associated with asthma predisposition (rs1801275: OR = 2.12; 95% CI = 1.39-3.22; P < 0.001*; rs1805010: OR = 1.6; 95% CI = 1.01-2.53; P < 0.05*; dominant model). Analysis of gender-genotype interactions, with genders nested within A/G-G/G, indicated higher odds for females than males of significant association with asthma (rs1801275: OR = 5.19, 95% CI = 2.09-12.94*; rs1805010: OR = 3.73, 95% CI = 2.06-6.74*). Rs1805010 and rs1801275 were in linkage disequilibrium (D' = 0.27; P < 0.0004*), with G-G haplotype being more frequent in asthmatics than in healthy subjects (OR = 2.43, 95% CI = 1.59-3.71*). CONCLUSIONS:The risk alleles, G, of IL-4R? rs1805010 and rs1801275 SNPs and corresponding A/G-G/G genotypes were significantly associated with asthma predisposition in asthmatics from Saudi Arabia.

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Potential role of Toll-like receptor 2 expression and polymorphisms in colon cancer susceptibility in the Saudi Arabian population.

Publications

Potential role of Toll-like receptor 2 expression and polymorphisms in colon cancer susceptibility in the Saudi Arabian population.

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