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, Aditya K.; Tripathy, Rina; Das, B. K.

doi:10.1177/0961203320972799

Cited by 11 publications

(5 citation statements)

References 36 publications

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“…The minor T allele frequencies in this study population and their significant association with different diseases are mentioned. The recent study from the eastern part (Odisha state) of India in all female subjects has shown an association of rs2569190 (C/T) SNP to increased predisposition to lupus (SLE) and the T-allele frequency was 0.46 for healthy control and 0.58 for SLE cases ( 37 ). The MAF (T allele) in other Indian studies are: West Bengal ( 38 ), 0.53, control vs. 0.49, Asthma case; Chennai ( 39 ), 0.43 in Control vs. 0.54 in Chronic periodontitis case; Hyderabad, Andhra Pradesh ( 40 ), 0.41 in Control vs. 0.53 in Ulcerative Colitis case; Chandigarh ( 41 ), 0.5 in Control vs. 0.64 in NAFLD case; and Lucknow, UP ( 42 ), 0.65 in healthy Control vs. 0.54 in CAD cases.…”

Section: Discussionmentioning

confidence: 99%

Pattern recognition receptor CD14 gene polymorphisms in alcohol use disorder patients and its Influence on liver disease susceptibility

et al. 2022

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BackgroundAlcohol use disorders (AUDs) leading to liver disease is major concern over other spectrum of disorder. Excessive alcohol consumption resulting in leaky gut syndrome is attributed to alcohol-induced liver injury through portal translocation of bacterial endotoxin. Susceptibility to alcoholic liver disease (ALD) in AUD patients could be dependent upon genes responsible for inflammation and alcohol metabolism. The pattern recognition receptor CD14 gene is a major player in endotoxin-mediated inflammation and susceptibility to ALD. This study investigated the genetic association of CD14 polymorphisms and other mechanisms relevant to altered inflammatory responses leading to ALD.MethodsPatients with alcohol use disorder with ALD (n = 128) and without liver disease (ALC, n = 184) and controls without alcohol use disorder (NALC, n = 152) from North India were enrolled. The CD4 gene polymorphisms in the North Indian population were evaluated by RFLP and sequencing. Secretory CD14 (sCD14), LBP, TLR4, MD2, TNFα, IL1b, IFNγ, IL6, IL10, and IL4 levels in serum were measured by ELISA among groups. The influence of polymorphisms on CD14 gene promoter activity and circulatory bacterial DNA level was determined.ResultsThe CD14 gene promoter and exonic region SNPs were found to be monomorphic, except for SNP rs2569190 for the North Indian population. The genetic association of SNP rs2569190(C/T) with the risk of developing ALD was found significant for TT genotype [ORTT, 95% CI = 2.19, 1.16–4.13 for ALD vs. ALC and OR, 2.09, 1.18–3.72 for ALD vs. NALC]. An increased sCD14 level was observed in AUD patients compared to NALC control. Increased levels of LBP, TLR4, TNFα, IL1β, IFNγ, and IL6 and reduced levels of MD2, IL10, and IL4 were observed among the ALD patients compared to the other two control groups. Elevated levels of pro-inflammatory and reduced levels of anti-inflammatory cytokines were observed in the risk genotype TT groups of ALD patients and the ALC group compared to NALC. Promoter activity was observed in the intronic region flanking SNPs and risk genotype can influence reporter activity, indicating CD14 gene expression.ConclusionEnhanced CD14 expression associated with inflammatory responses increases susceptibility to ALD in the TT genotype of AUD patients.

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Section: Discussionmentioning

confidence: 99%

Pattern recognition receptor CD14 gene polymorphisms in alcohol use disorder patients and its Influence on liver disease susceptibility

et al. 2022

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“…It is worth noting that by using our smartphone-based app, we were able to accurately detect serum soluble CD14 as a potential disease-activity-related biomarker of lupus [ 45 , 46 ]. sCD14 concentrations in patients with lupus nephritis were reported around 2~10 mg/L in plasma [ 47 , 48 ]. In this assay, CD14 captures the antibody and detection antibody were used to form a sandwich structure with the analyte to detect CD14 in a microarray format.…”

Section: Resultsmentioning

confidence: 99%

Smartphone-Based Quantitative Analysis of Protein Array Signals for Biomarker Detection in Lupus

Yang

Tang

et al. 2022

Chemosensors

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Fluorescence-based microarray offers great potential in clinical diagnostics due to its high-throughput capability, multiplex capabilities, and requirement for a minimal volume of precious clinical samples. However, the technique relies on expensive and complex imaging systems for the analysis of signals. In the present study, we developed a smartphone-based application to analyze signals from protein microarrays to quantify disease biomarkers. The application adopted Android Studio open platform for its wide access to smartphones, and Python was used to design a graphical user interface with fast data processing. The application provides multiple user functions such as “Read”, “Analyze”, “Calculate” and “Report”. For rapid and accurate results, we used ImageJ, Otsu thresholding, and local thresholding to quantify the fluorescent intensity of spots on the microarray. To verify the efficacy of the application, three antigens each with over 110 fluorescent spots were tested. Particularly, a positive correlation of over 0.97 was achieved when using this analytical tool compared to a standard test for detecting a potential biomarker in lupus nephritis. Collectively, this smartphone application tool shows promise for cheap, efficient, and portable on-site detection in point-of-care diagnostics.

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“…On the genetic level, a polymorphism was recognized inside the CD14 gene promoter sequence with a C–T transition at base pair-159 from the main transcription start site [ 21 ]. The wild type was (CC), while the homozygous mutant was (TT), and the heterozygous mutant was (CT) [ 22 ]. Several studies reported the association between this polymorphism and allergic diseases [ 23 , 24 ].…”

Section: Discussionmentioning

confidence: 99%

Association of serum CD14 level and functional polymorphism C-159T in the promoter region of CD14 gene with allergic rhinitis

Kamel,

Selim,

Tantawy

et al. 2023

Clin Exp Med

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Allergic rhinitis (AR) is an inflammatory disease of the upper respiratory tract affecting a significant number of the world’s population. It occurs as an IgE-mediated immune response of the nasal mucosa to inhaled allergens. The human Cluster of Differentiation 14 (CD14) is a glycosyl-phosphatidylinositol-anchored molecule expressed on the surface of monocytes and macrophages and functions as a receptor to lipopolysaccharides and inhaled endotoxins that may stimulate interleukins production by antigen-presenting cells. Consequently, CD14 plays a substantial role in allergic diseases and may become one of their etiological causes. Allergic rhinitis (AR) is an inflammatory disease of the upper respiratory tract affecting a significant number of the world’s population. It occurs as an IgE-mediated immune response of the nasal mucosa to inhaled allergens. The human Cluster of Differentiation 14 (CD14) is a glycosyl-phosphatidylinositol-anchored molecule expressed on the surface of monocytes and macrophages and functions as a receptor to lipopolysaccharides and inhaled endotoxins that may stimulate interleukins production by antigen-presenting cells. Consequently, CD14 plays a substantial role in allergic diseases and may become one of their etiological causes. This study aimed to determine the association between C-159T polymorphism in the CD14 gene promoter region and serum CD14 levels and the risk of Allergic rhinitis Egyptian patients and to test the validity of serum CD14 level measurement in predicting AR. This case–control study included 45 patients with AR referred to Allergy and Immunology Unit, Zagazig University Hospital, Zagazig, Egypt, and 45 healthy subjects as controls. Serum CD14 levels were measured by ELISA. The polymerase chain reaction-restriction fragment length polymorphism technique was used to detect C-159T gene polymorphism in the CD14 promoter region. This case–control study included 45 patients with AR referred to Allergy and Immunology Unit, Zagazig University Hospital, Zagazig, Egypt, and 45 healthy subjects as controls. Serum CD14 levels were measured by ELISA. The polymerase chain reaction-restriction fragment length polymorphism technique was used to detect C-159T gene polymorphism in the CD14 promoter region. There was a significant association between CD14 serum levels and AR incidence (P < 0.001), with patients having higher serum CD14 levels than controls. In addition, a significant association (P < 0.001) was detected between serum CD14 levels and the severity of AR, as well as elevated serum CD14 levels in severe and the most severe cases. On the molecular level, there was a statistically significant relationship between patients and the control group regarding the CD14 genotype (P < 0.001), where CT and TT genotypes and T allele were primarily associated with the cases group, indicating that the risk of AR was significantly associated with the inheritance of the TT genotype. Additionally, a statistically significant association was found between the severity of AR and CD14 genotype (P < 0.001), where TT genotypes were mainly associated with severe and the most severe cases. In the studied groups, there was a statistically significant difference (P < 0.05) between the CD14 genotype and serum CD14 levels, with TT genotypes being associated with higher CD14 levels. The results obtained in this study revealed that serum CD14 level is a potential biomarker for the diagnosis of AR and, at the genetic level, a potential predictor of disease.

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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

Cited by 11 publications

References 36 publications

Pattern recognition receptor CD14 gene polymorphisms in alcohol use disorder patients and its Influence on liver disease susceptibility

Pattern recognition receptor CD14 gene polymorphisms in alcohol use disorder patients and its Influence on liver disease susceptibility

Smartphone-Based Quantitative Analysis of Protein Array Signals for Biomarker Detection in Lupus

Association of serum CD14 level and functional polymorphism C-159T in the promoter region of CD14 gene with allergic rhinitis

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