TLR-4 and CD14 Genotypes and Soluble CD14: Could They Predispose to Coronary Atherosclerosis?

Konstantinidou, Maria Kalliopi; Goutas, Nikos; Vlachodimitropoulos, Dimitrios; Chaidaroglou, Antigoni; Stefanou, Demetrios; Poumpouridou, Nikoleta; Mastorakou, Renata; Gazouli, Maria; Kyparissopoulos, Dimitrios; Spiliopoulou, Chara

doi:10.3390/jcdd3010009

Cited by 4 publications

(2 citation statements)

References 53 publications

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“…More specifically, genomic DNA from peripheral blood was isolated using a NucleoSpin Blood kit (Macherey–Nagel, GmbH & Co. KG, Düren, Germany) according to the manufacturer’s instructions. Genotyping in all selected polymorphisms was performed by PCR-RFLP analysis for the TLR-4 Asp299Gly (rs4986790) and TLR-4 Thr399Ile (rs4986791) polymorphisms, as previously described [ 63 ]. Specific, primers for TLR-4 Asp299Gly were: forward (5′-GATTAGCATACTTAGACTACTACCTCCATG-3′) and reverse (5′-GATCAACTTCTGAAAAAGCATTCCCAC-3′) and for TLR-4 Thr399Ile were forward (5′-GGTTGCTGTTCTCAAAGTGATTTTGGGAGAA-3′) and reverse (5′-CCTGAAGA CTGGAGAGTGAGTTAAATGCT-3′).…”

Section: Methodsmentioning

confidence: 99%

Single Nucleotide Polymorphisms of Toll-like Receptor 4 in Hepatocellular Carcinoma—A Single-Center Study

Ανδρουτσάκος

Bakasis

Pouliakis

et al. 2022

IJMS

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Hepatocellular carcinoma (HCC) is the most common primary liver tumor leading to significant morbidity and mortality; its exact genetic background is largely unrecognized. Toll-like receptor-4 (TLR4) reacts with lipopolysaccharides, molecules found in the outer membrane of Gram-negative bacteria. In damaged liver, TLR4 expression is upregulated, leading to hepatic inflammation and injury. We tried to investigate the role of the two most common single-nucleotide polymorphisms (SNPs) of TLR4 in HCC-genesis. Aged > 18 years old, cirrhotic patients were included in this study. Exclusion criteria were non-HCC tumors and HIV co-infection. TLR4 SNPs association with HCC occurrence was the primary endpoint, and associations with all-cause and liver-related mortality, as well as time durations between diagnosis of cirrhosis and HCC development or death and diagnosis of HCC and death were secondary endpoints. A total of 52 out of 260 included patients had or developed HCC. TLR4 SNPs showed no correlation with primary or secondary endpoints, except for the shorter duration between HCC development and death in patients with TLR4 mutations. Overall, TLR4 SNPs showed no correlation with carcinogenesis or deaths in patients with liver cirrhosis; patients with TLR4 SNPs that developed HCC had lower survival rates, a finding that should be further evaluated.

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Section: Methodsmentioning

confidence: 99%

Single Nucleotide Polymorphisms of Toll-like Receptor 4 in Hepatocellular Carcinoma—A Single-Center Study

Ανδρουτσάκος

Bakasis

Pouliakis

et al. 2022

IJMS

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“…Some clinical studies have demonstrated that the effects of polymorphisms of genetic variants of the human TLR4 gene, located on chromosome 9, on the progression of the atherosclerosis, is controversial (12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

Genetic Variants of Toll Like Receptor-4 in Patients with Premature Coronary Artery Disease, South of Iran

Erfanian¹,

Shojaei²,

Mehdizadeh³

2017

ME-JFM

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Introduction: Ischemic cardiovascular diseases are the leading causes of morbidity and mortality in most developed and developing countries including Iran. Premature myocardial infarction has a polygenic base with a complex relation with environmental factors. Since expression of different inflammatory genes especially toll like receptor-4 (TLR4) has increased considerably in human atherosclerotic plaques, we have decided to study variants of TLR4 in premature coronary artery disease in patients in Jahrom city, Iran. Methods: In this case-control study, 100 patients with a history of premature coronary artery diseases and 100 healthy control subjects referred to health centers in Jahrom city were studied. Target sequences of TLR4 gene were amplified by PCR amplification and digestion was done by StyI restriction enzyme (PCR-RFLP method). Results: There was no significant difference regarding age (P>0.05). The distribution of TC heterozygote genotype in the premature myocardial infarction group is significantly higher than in the healthy group (P<0.05) but the homozygote mutated genotype showed no significant difference (P>0.05). In addition, the genotype carrying the mutated allele (TC+CC) showed a significant difference when compared to TC variant (P < 0.05). The genotype distribution in rs1927911 in both genders shows no concomitance between males and females (P>0.05). Conclusion: According to the results derived from this study, it seems like the existence of the genotype carrying the mutated allele (TC+CC) in rs1927911's mononucleotide polymorphism of TLR gene is associated with an increased risk of premature myocardial infarction.

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Investigation of associations of ARMS2, CD14, and TLR4 gene polymorphisms with wet age-related macular degeneration in a Greek population

Sarli

Skalidakis

Velissari

et al. 2017

OPTH

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BackgroundAge-related macular degeneration (AMD) is a multifactorial degenerative ocular disease that leads to loss of central vision. Functional gene polymorphisms have already been associated with the disease (for example, ARMS2 A69S, rs10490924).AimThe goal of our study was to verify the correlation of the aforementioned ARMS2 variation with the disease, to examine, for the first time, the role of the CD14 C260T variation (rs2569190), and to investigate the association of two TLR4 polymorphisms (Asp299Gly or rs4986790 and Thr399Ile or rs4986791) in a Greek population with the wet form of AMD.Patients and methodsGenomic DNAs were isolated from blood samples of 103 healthy controls and 120 Greek patients with wet AMD who were age- and sex-matched, and all of whom were clinically evaluated. For the genotyping of all selected polymorphisms, polymerase chain reaction–restriction fragment length polymorphism analysis was performed.Results and conclusionsThis study confirmed the association between the ARMS2 variation and AMD, detecting the T risk allele in a significantly higher frequency in the patient group, compared with the control subjects (45% vs 29.13%, P<0.001, odds ratio [OR] 1.99, confidence interval 1.34–2.95). For the CD14 polymorphism, no statistically significant correlation was observed. As for the TLR4 polymorphisms, the percentage of heterozygotes increased from 2.9% to 11.7% in the patient population for Asp299Gly and from 1.9% to 10% for the Thr399Ile polymorphism (ORs 4.40 [P=0.01] and 5.61 [P=0.0088], respectively). Although our ARMS2 and CD14 results provided definite conclusions, the role of innate immunity TLR4 gene awaits further investigation in larger AMD populations with more clinical data collected on past microbial infections.

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TLR-4 and CD14 Genotypes and Soluble CD14: Could They Predispose to Coronary Atherosclerosis?

Cited by 4 publications

References 53 publications

Single Nucleotide Polymorphisms of Toll-like Receptor 4 in Hepatocellular Carcinoma—A Single-Center Study

Single Nucleotide Polymorphisms of Toll-like Receptor 4 in Hepatocellular Carcinoma—A Single-Center Study

Genetic Variants of Toll Like Receptor-4 in Patients with Premature Coronary Artery Disease, South of Iran

Investigation of associations of <em>ARMS2</em>, <em>CD14</em>, and <em>TLR4</em> gene polymorphisms with wet age-related macular degeneration in a Greek population

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