Dataset Information

Toll-like receptor 4 polymorphisms in Saudi population with cardiovascular diseases.

ABSTRACT: BACKGROUND:Toll-like receptors play a substantial role in innate immunity and the effects of TLR4 genetic variants on cardiovascular diseases are still largely unknown. Therefore, we aimed to investigate the effects of TLR4 polymorphisms on cardiovascular diseases risk in the Saudi population. METHODS:Three tag single-nucleotide polymorphisms (rs2770150, rs10759931, and rs4986790) in TLR4 were studied on 222 unrelated patients with cardiovascular diseases and 190 healthy volunteers. RESULTS:We found that, in patients over 60 years old, the frequency of the TT genotype in rs2770150 and the variant allele G in rs10759931 were higher compared to the control group. Based on gender, the genotype frequency of rs2770150 increases the risk for cardiovascular diseases in female patients by 3.6-fold. The allele frequency for the G allele of rs10759931 increased the risk for CVDs in male patients by more than 1.5-fold. Furthermore, the genotype frequency of rs2770150 had a significant association with cardiovascular diseases in patients without hypertension and G allele of rs10759931 significantly increased the risk of cardiovascular diseases in patients that smoked. After Bonferroni correction only patients without hypertension showed significant risk of CVD with rs2770150. CONCLUSION:A deeper understanding of the genetic variability of TLR4 will enable us to better identification of biomarkers for early detection and prognosis, and also enhance the decision-making process of treatments for cardiovascular diseases.

SUBMITTER: Semlali A

PROVIDER: S-EPMC7650605 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Toll-like receptor 4 polymorphisms in Saudi population with cardiovascular diseases.

Semlali Abdelhabib A Al Mutairi Mikhlid M Oqla Alanazi Ibrahim I Awad Aljohi Hasan H Reddy Parine Narasimha N Alhadheq Abdullah A Al-Jafari Abdulaziz A AA Mobeirek Abdulelah F AF Al Amri Abdullah A Shaik Jilani P JP Filali Fatima-Zohra FZ Alanazi Mohammad M

Molecular genetics & genomic medicine 20190721 9

<h4>Background</h4>Toll-like receptors play a substantial role in innate immunity and the effects of TLR4 genetic variants on cardiovascular diseases are still largely unknown. Therefore, we aimed to investigate the effects of TLR4 polymorphisms on cardiovascular diseases risk in the Saudi population.<h4>Methods</h4>Three tag single-nucleotide polymorphisms (rs2770150, rs10759931, and rs4986790) in TLR4 were studied on 222 unrelated patients with cardiovascular diseases and 190 healthy volunteer ...[more]

PMID: 31328431

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Project description: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.

Project description:Background and objective: On the basis that the inflammatory effects of TNF (tumour necrosis factor) are predominantly mediated through interaction with the TNF receptor-1 (TNFRSF1A), the current study was designed to establish the prevalence of the mutations, R92Q and P46L TNFRSF1A polymorphisms both in the general healthy Saudi population, and in Saudi patients carrying inflammatory diseases such as atherosclerosis or rheumatoid arthritis. We felt it important to report the frequency of the mutations, R92Q and P46L TNFRSF1A polymorphisms in healthy Saudi individuals, and those with inflammatory conditions, as well as to describe the pattern of immunological factors in individuals expressing R92Q or P46L TNFRSF1A. Patients and methods: We collected in PAX gene blood RNA tubes (for RT-PCR and sequencing) 500 blood samples from normal healthy individuals from the West and Center of Saudi Arabia, as well as 100 from patients with atherosclerosis, and 100 patients diagnosed with rheumatoid arthritis. All were screened for the levels of soluble TNF, C-reactive protein (CRP), interleukin6 (IL-6) and sTNFR1. In addition, they were screened for R92Q and P46L TNFRSF1A by RT-PCR. Moreover, phenotype and expression of peripheral blood mononuclear cells (PBMCs) was performed by flow cytometry (FACS). Results: Across 500 normal individuals, 8 (1.6%) expressed both R92Q and P46L mutations. By contrast, of the 100 patients in our study with atherosclerosis, 34% expressed both the R92Q and P46L mutations, whilst 42% of patients with rheumatoid arthritis expressed both mutations R92Q and P46L. No significant differences were observed between cell markers of normal individuals (CD3, 4, 8, 16, 56, 19, 25, ICAM-1, VLA-4 & l-selectin) and patients with atherosclerosis. There were significantly high values of cell markers in patients with rheumatoid arthritis compared with normal individuals both in terms of percentage and absolute counts (p < 0.05). Soluble IL-6 and sTNFR1 showed significant decreases in atherosclerosis and rheumatoid arthritis when compared with controls (p < 0.05). In addition, CRP and sTNF showed significant increases in the atherosclerosis and rheumatoid arthritis groups when compared to controls (p < 0.05). Conclusion: Our findings reasonably anticipate the presence of TRAPS disease (low penetrance mutations) amongst the Saudi population although further studies are needed to confirm these results.

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Toll-like receptor 4 polymorphisms in Saudi population with cardiovascular diseases.

Publications

Toll-like receptor 4 polymorphisms in Saudi population with cardiovascular diseases.

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