Interleukin-18 promoter −137 G/C polymorphism (rs187238) is associated with biochemical markers of renal function and cardiovascular disease in type 2 diabetes patients

Cavalcante, Jânio Emanuel Andrade; Sousa, Ederson Laurindo Holanda de; Rodrigues, Rodrigo Rodrigues; Viana, Glautemberg de Almeida; Gadelha, Daniel Duarte; Carvalho, Manoela Montenegro Dias de; Sousa, Duaran Lopes; Silva, Allysson Jordan Xavier; Filho, Raimundo Rigoberto Barbosa Xavier; Fernandes, Virgínia Oliveira; Júnior, Renan Magalhães Montenegro; Alves, Renata de Sousa; Meneses, Gdayllon Cavalcante; Sampaio, Tiago Lima; Queiroz, Maria Goretti Rodrigues de

doi:10.1016/j.clinbiochem.2020.03.011

Cited by 10 publications

(4 citation statements)

References 59 publications

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“…Pathway analysis (GSEA) comparing DE genes enriched in IM-ASC compared to FA-ASC demonstrated increased inflammatory response pathways, TNFA signaling, and TGFβ signaling (Figure 3D, Table S3). IM-ASC specific inflammatory genes included IL16 and IL18 previously implicated in metabolic disease [29][30][31][32] suggesting that IM-ASC-derived IL-18 and IL-16 may contribute to VAT dysfunction.…”

Section: Depot Specific Differences In Adipose Stromal Cells (Asc)mentioning

confidence: 99%

Single-nuclei Transcriptome of Human AT Reveals Metabolically Distinct Depot-Specific Adipose Progenitor Subpopulations

Barboza

Flesher

Geletka

et al. 2022

Preprint

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Single-cell and single-nuclei RNA sequencing data (scRNAseq and snRNAseq, respectively) have revealed substantial heterogeneity in the AT (AT) cellular landscape in rodents and humans depending on depot and disease status. We used snRNAseq to characterize the cellular landscape of human visceral (VAT) and subcutaneous AT (SAT) samples from lean subjects and subjects with obesity. We identified multiple cell types in the AT cellular repertoire, including three major AT stromal cell (ASC) subpopulations, multiple types of adipocyte (ADIPO) populations that retain properties similar to ASC, endothelial cell (EC), T-cell, and macrophage (MAC) populations that are in concordance and expand upon other published datasets. ADIP and EC are more prominent in SAT compared to VAT which has a higher proportion of ASC. Of two dominant ASC subpopulations, one (inflammatory-mesothelial, IM-ASC) is present in VAT, but absent in SAT, while the other (fibroadipogenic, FA-ASC) is present in both VAT and SAT. Both populations retain their properties in in vitro culture and have adipogenic capacity with different metabolic features. Informatic and in situ studies support ADIP derived from IM- and FA-ASC are found in human VAT. We also identified a wide range of EC subtypes in human AT with features of lymphatic, venous, and arterial EC, with identification of a PRDM16 expression EC population with features of an EC progenitor. Immune cell populations match recent experimental validation of lipid activated macrophage (LAM) phenotypes, TIM4 macrophages, and a prominent population of MRC1/CD206+ resident AT macrophages with gene expression signatures related to glucocorticoid activation. Overall, our study demonstrates depot-specific cellular diversity in human VAT and SAT in which distinct ASC subpopulations may differently contribute to AT dysfunction in obesity. Also, our results highlight an unprecedented EC heterogeneity suggesting AT EC as highly specialized cells and potentially important regulators of depot-specific functions.

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Section: Depot Specific Differences In Adipose Stromal Cells (Asc)mentioning

confidence: 99%

Single-nuclei Transcriptome of Human AT Reveals Metabolically Distinct Depot-Specific Adipose Progenitor Subpopulations

Barboza

Flesher

Geletka

et al. 2022

Preprint

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“…The G-to-C substitution at position -137 (rs187238) of IL-18 gene insert a histone 4 transcription factor-1 (H4TF-1) nuclear factorbinding site. Functional assays have previously demonstrated that the rs187238G allele is associated with increased production of IL-18 [31,45] and correlates with increased IL-18 levels in peripheral blood mononuclear cells or plasma [46]. In this view might be of a certain interest that IL-18 levels are considered useful markers of ARDS in COVID-19 and other clinical conditions [47][48][49].…”

Section: Discussionmentioning

confidence: 95%

IL-1 Superfamily Member (IL-1A, IL-1B and IL-18) Genetic Variants Influence Susceptibility and Clinical Course of Mediterranean Spotter Fever

et al. 2022

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Mediterranean Spotted Fever (MSF) is one of the most common spotted fever Rickettsioses. Most cases of MSF follow a benign course, with a minority of cases being fatal. The severity of the infection depends on bacterial virulence, dose and host factors such as effective immune response and genetic background. Herein, we reported data on typing by competitive allele-specific PCR of functionally relevant polymorphisms of genes coding for MyD88 adapter-like (Mal/TIRAP) protein (rs8177374), interleukin(IL)-1 cluster (IL-1A rs1800587, IL-1B rs16944 and rs1143634) and IL-18 (rs187238), which might be crucial for an efficient immune response. The results enlighten the role that IL-1 gene cluster variants might play in susceptibility against Rickettsia conorii infection. In particular, the IL-1A rs1800587TT genotype was significantly increased in patients alone and combined in a haplotype composed by minor alleles rs1800587T, rs16944A and rs1143634A. This result was confirmed using the decision tree heuristic approach. Using this methodology, IL-1A rs1800587TT genotype was the better discrimination key among MSF patients and controls. In addition, the IL-1 gene cluster SNP genotypes containing minor alleles and IL-18 rs187238G positive genotypes were found as associated with risk of severe complications such as sepsis, septic shock, acute respiratory distress syndrome and coma. In conclusion, these data suggest that the evaluation of IL-1A, IL-1B and IL-18 gene SNPs can add useful information on the clinical course of patients affected by Mediterranean Spotted Fever, even if further confirmatory studies will be necessary.

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“…An acute phase protein, a biomarker of the inflammatory reaction and an important risk marker for CVD [20] Interleukin (IL)-6 A pro-inflammatory cytokine, anti-inflammatory myokine and inducer of CRP synthesis, associated with increased CVR [21] Tumour necrosis factor (TNF)-α A pro-inflammatory cytokine that accelerates the progression of CVDs [22] Interleukin (IL)-1 A cytokine extremely expressed in several CVDs and contributes to their pathogenesis [23] Interleukin (IL)-11-receptor antagonist A stromal cell-derived cytokine capable of both pro-and antiinflammatory ability linked to CVR [24] Interleukin (IL)-10 An anti-inflammatory cytokine, stimulating inflammatory resolution and deflects endothelial dysfunction [25] Interleukin (IL)-18 A pro-inflammatory cytokine that stimulates interferon (IFN)-γ production and a link to CVR [26] Neopterin A pteridine that indicates pro-inflammatory immune status, disease severity and prognosis in CVD [27]…”

Section: Biomarker Descriptionmentioning

confidence: 99%

Genetic Polymorphisms and Their Interactions with the Risk Factors of Cardiovascular Diseases: Review Chapter

Chalwe¹,

Grobler²,

Oldewage‐Theron³

2022

Risk Factors for Cardiovascular Disease

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Cardiovascular diseases (CVDs) have been reported to have a complex pathogenesis by a number of studies. Atherosclerosis and inflammation have been established as the main contributors to CVDs. Furthermore, genetic polymorphisms have been identified and found to have a correlation with an individual’s susceptibility to developing CVD. Some of these polymorphisms and corresponding cardiovascular risk (CVR) factors include: C174G (Interleukin (IL)-6 association), methylenetetrahydrofolate reductase (MTHFR) C667T/A1298C (hyperhomocysteinaemia), VII R353Q (coagulation factor VII association) and rs247616/rs1968905/rs1270922 (cholesteryl ester transfer protein (CEPT) - cholesterol metabolism) amongst others. At a time when disease prediction, diagnosis and prognosis are still being investigated, these polymorphisms have the potential for use in these areas as well as opening more opportunities in the understanding of CVD. The objective of this chapter was to review the current knowledge about the relationship between genetic polymorphisms and cardiovascular disease.

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Interleukin-18 promoter −137 G/C polymorphism (rs187238) is associated with biochemical markers of renal function and cardiovascular disease in type 2 diabetes patients

Cited by 10 publications

References 59 publications

Single-nuclei Transcriptome of Human AT Reveals Metabolically Distinct Depot-Specific Adipose Progenitor Subpopulations

Single-nuclei Transcriptome of Human AT Reveals Metabolically Distinct Depot-Specific Adipose Progenitor Subpopulations

IL-1 Superfamily Member (IL-1A, IL-1B and IL-18) Genetic Variants Influence Susceptibility and Clinical Course of Mediterranean Spotter Fever

Genetic Polymorphisms and Their Interactions with the Risk Factors of Cardiovascular Diseases: Review Chapter

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