The CD14 (−159 C/T) SNP is associated with sCD14 levels and allergic asthma, but not with CD14 expression on monocytes

Nieto‐Fontarigo, Juan José; Salgado, FJ; San-José, ME; Cruz, María-Jesús; Casas-Fernández, A.; Gómez-Conde, M. J.; Valdés-Cuadrado, Luís; García-González, MA; Arias, Pilar; Nogueira, Marco Aurélio; González-Barcala, FJ

doi:10.1038/s41598-018-20483-1

Cited by 16 publications

(17 citation statements)

References 47 publications

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“…Mutants displayed higher sCD14 compared to wild type (CC), which corroborates with earlier observations. 11,12,31 A similar observation was also noted for plasma levels of TNF-α and IFN-α. The transition polymorphism (C > T) at the promoter region decreases Sp protein binding efficiency and enhances transcription levels of CD14, leading to a higher level of sCD14.…”

Section: Discussionsupporting

confidence: 73%

CD14 (C-159T) polymorphism is associated with increased susceptibility to SLE, and plasma levels of soluble CD14 is a novel biomarker of disease activity: A hospital-based case-control study

Panda

Tripathy²,

Das

2020

Lupus

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Background Cluster of differentiation 14 (CD14) plays a crucial role in the innate immune response of the host in protection against various pathogens. The importance of soluble CD14 in autoimmune disorders has been described in different populations. However, the role of sCD14 in systemic lupus erythematosus (SLE) is poorly understood. Further, the association of functional variants at the promoter region of the CD14 gene (−159 C > T) with susceptibility to SLE or disease severity needs to be defined. Methods Two hundred female SLE patients diagnosed on systemic lupus international collaborating clinics (SLICC) classification criteria and age, sex, matched healthy controls were enrolled in the present study. Polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) method was used to genotype CD14 (C-159 T) polymorphism. Plasma levels of IFN-α, TNF-α, and sCD14 were quantified by enzyme-linked immunosorbent assay (ELISA). Results Prevalence of mutant genotypes (CT and TT) and minor allele (T) of CD14 (C-159T) polymorphism was significantly higher in SLE cases compared to healthy controls (CT: P < 0.0001; OR = 3.26, TT:P < 0.0001; OR = 3.39; T:P = 0.0009, OR = 1.62). Further, lupus nephritis patients had a higher prevalence of homozygous mutants (TT) and mutant allele (T)(TT: P = 0.0002, OR = 8.07; T: P = 0.001, OR = 1.32). SLE patients displayed significantly increased plasma sCD14, TNF-α, and IFN-α levels in comparison to healthy controls. These cytokines were significantly elevated in patients of lupus nephritis compared to those without kidney involvement. Interestingly, sCD14 levels correlated positively with SLE disease activity index-2K (SLEDAI-2K) scores and 24 hours proteinuria. Conclusion CD14 (C-159T) polymorphism is associated with an increased predisposition to the development of SLE and lupus nephritis: sCD14 is a promising novel biomarker for assessing disease activity and lupus nephritis.

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Section: Discussionsupporting

confidence: 73%

CD14 (C-159T) polymorphism is associated with increased susceptibility to SLE, and plasma levels of soluble CD14 is a novel biomarker of disease activity: A hospital-based case-control study

Panda

Tripathy²,

Das

2020

Lupus

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“…IFN-γ is an essential cytokine for the control of mycobacterial infection [36], and for that reason it is possible to hypothesize that rs2569190 may result in an environment that favors development of TB. Interestingly, other studies also related this SNP with occurrence of ischemic stroke [37], cardiovascular disease [38] and asthma [39], indicating that these polymorphisms could actually lead to a more profound alteration in immune responses that may affect a large number of clinical conditions.…”

Section: Discussionmentioning

confidence: 96%

The Influence of Single Nucleotide Polymorphisms of NOD2 or CD14 on Susceptibility to Tuberculosis: A Systematic Review

Angulo

Fernandes

Araújo

et al. 2020

Preprint

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Background: Tuberculosis (TB) is still one of the leading causes of death worldwide. Genetic studies have pointed to the relevance of the NOD2 and CD14 polymorphic alleles in association with susceptibility or resistance to TB. Methods: A systematic review was performed on search platforms to examine the association between single nucleotide polymorphisms (SNP) and TB risk. Study quality was evaluated using the Newcastle-Ottawa Quality Scale (NOQS) Results: Thirteen studies matched the selection criteria. Of those, 9 investigated CD14 SNPs, and 6 reported a significant association between the T allele and TT genotypes of the rs2569190 SNP and increased TB risk. In contrast, the genotype CC was found to be protective against the disease. Furthermore, in two studies, rs2569191 SNP of the CD14, G allele was described to be significantly associated with increased TB risk. Four studies reported data uncovering the relationship between NOD2 SNPs and TB risk, with two of them reporting significant associations of rs1861759 and rs7194886 and higher TB risk in a Chinese Han population. Paradoxically, minor allele carriers (CG or GG) of rs2066842 and rs2066844 NOD2 SNPs were associated with lower TB risk in African Americans. Conclusions: The CD14 rs2569190 and rs2569191 polymorphisms influence TB risk depending on the allele. Furthermore, there is significant association between NOD2 SNPs rs1861759 and rs7194886 and augmented risk of TB, especially in persons with Chinese ethnicity. The referred polymorphisms of CD14 and NOD2 genes likely play an important role in TB susceptibility and physiopathology; such effect may be affected by ethnicity.Systematic review registration: CRD42020186523

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“…Soluble CD14 (sCD14) is a pattern recognition receptor and acts as a co-receptor of TLR-4 to bind microbial components to endothelial and epithelial cells [99]. The risk allele T of rs2569190 for pneumococcal disease susceptibility in our meta-analysis, is associated with high sCD14 levels in expression studies [100, 101]. Our findings correspond with other studies showing the T allele is associated with an increased occurrence of sepsis and increased serum sCD14 levels in patients with risk genotypes [102] [103].…”

Section: Discussionmentioning

confidence: 99%

Host genetic variability and pneumococcal disease: a systematic review and meta-analysis

2019

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Background Pneumonia, sepsis, meningitis, and empyema due to Streptococcus pneumoniae is a major cause of morbidity and mortality. We provide a systemic overview of genetic variants associated with susceptibility, phenotype and outcome of community acquired pneumococcal pneumonia (CAP) and invasive pneumococcal disease (IPD). Methods We searched PubMed for studies on the influence of host genetics on susceptibility, phenotype, and outcome of CAP and IPD between Jan 1, 1983 and Jul 4, 2018. We listed methodological characteristics and when genetic data was available we calculated effect sizes. We used fixed or random effect models to calculate pooled effect sizes in the meta-analysis. Results We identified 1219 studies of which 60 studies involving 15,358 patients were included. Twenty-five studies (42%) focused on susceptibility, 8 (13%) on outcome, 1 (2%) on disease phenotype, and 26 (43%) on multiple categories. We identified five studies with a hypothesis free approach of which one resulted in one genome wide significant association in a gene coding for lincRNA with pneumococcal disease susceptibility. We performed 17 meta-analyses of which two susceptibility polymorphisms had a significant overall effect size: variant alleles of MBL2 (odds ratio [OR] 1·67, 95% confidence interval [CI] 1·04–2·69) and a variant in CD14 (OR 1·77, 95% CI 1·18–2·66) and none of the outcome polymorphisms. Conclusions Studies have identified several host genetics factors influencing risk of pneumococcal disease, but many result in non-reproducible findings due to methodological limitations. Uniform case definitions and pooling of data is necessary to obtain more robust findings.

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The CD14 (−159 C/T) SNP is associated with sCD14 levels and allergic asthma, but not with CD14 expression on monocytes

Cited by 16 publications

References 47 publications

CD14 (C-159T) polymorphism is associated with increased susceptibility to SLE, and plasma levels of soluble CD14 is a novel biomarker of disease activity: A hospital-based case-control study

CD14 (C-159T) polymorphism is associated with increased susceptibility to SLE, and plasma levels of soluble CD14 is a novel biomarker of disease activity: A hospital-based case-control study

The Influence of Single Nucleotide Polymorphisms of NOD2 or CD14 on Susceptibility to Tuberculosis: A Systematic Review

Host genetic variability and pneumococcal disease: a systematic review and meta-analysis

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