Serpin Family E Member 1 Tag Single-Nucleotide Polymorphisms in Patients with Diabetic Nephropathy: An Association Study and Meta-Analysis Using a Genetic Model-Free Approach

Tziastoudi, Maria; Dardiotis, Efthimios; Pissas, Georgios; Filippidis, Georgios; Golfinopoulos, Spyridon; Siokas, Vasileios; Tachmitzi, Sophia V.; Eleftheriadis, Theodoros; Hadjigeorgiou, Georgios M.; Tsironi, Evangelia E.; Stefanidis, Ioannis

doi:10.3390/genes12121887

Cited by 6 publications

(6 citation statements)

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“…The SERPINE1 polymorphisms evaluated in this study included rs2227631 (-1844 G/A), which is located in the promoter region and has been implicated as a regulatory region variant with possible functional loci; however, functional studies are necessary to explore the specific effects on COVID-19 severity ( 18 ). Furthermore, rs2227667, rs2070682, and rs2227692, located in intronic regions, were also analyzed ( 14 ).…”

Section: Discussionmentioning

confidence: 99%

“…The SERPINE1 gene is located on chromosome 7q22.1, and some polymorphisms in the SERPINE1 promoter region have been associated with severe COVID-19 ( 13 , 14 ) as well as with a suboptimal fibrinolytic response ( 15 , 16 ).…”

Section: Introductionmentioning

confidence: 99%

“…rs2227631 is located in the promoter and is implicated in PAI regulation. rs5557667 is located in the intronic region between exons 3-4, rs2070682 is located in introns 5-6, and rs222692 is located in introns 7-8 ( 14 , 18 ).…”

Section: Introductionmentioning

confidence: 99%

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The fatal contribution of serine protease-related genetic variants to COVID-19 outcomes

Martínez-Gómez,

Martinez-Armenta,

Tusie-Luna

et al. 2024

Front. Immunol.

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IntroductionSerine proteases play a critical role during SARS-CoV-2 infection. Therefore, polymorphisms of transmembrane protease serine 2 (TMPRSS2) and serpine family E member 1 (SERPINE1) could help to elucidate the contribution of variability to COVID-19 outcomes.MethodsTo evaluate the genetic variants of the genes previously associated with COVID-19 outcomes, we performed a cross-sectional study in which 1536 SARS-CoV-2-positive participants were enrolled. TMPRSS2 (rs2070788, rs75603675, rs12329760) and SERPINE1 (rs2227631, rs2227667, rs2070682, rs2227692) were genotyped using the Open Array Platform. The association of polymorphisms with disease outcomes was determined by logistic regression analysis adjusted for covariates (age, sex, hypertension, type 2 diabetes, and obesity).ResultsAccording to our codominant model, the GA genotype of rs2227667 (OR=0.55; 95% CI = 0.36-0.84; p=0.006) and the AG genotype of rs2227667 (OR=0.59; 95% CI = 0.38-0.91; p=0.02) of SERPINE1 played a protective role against disease. However, the rs2227692 T allele and TT genotype SERPINE1 (OR=1.45; 95% CI = 1.11-1.91; p=0.006; OR=2.08; 95% CI = 1.22-3.57; p=0.007; respectively) were associated with a decreased risk of death. Similarly, the rs75603675 AA genotype TMPRSS2 had an OR of 1.97 (95% CI = 1.07-3.6; p=0.03) for deceased patients. Finally, the rs2227692 T allele SERPINE1 was associated with increased D-dimer levels (OR=1.24; 95% CI = 1.03-1.48; p=0.02).DiscussionOur data suggest that the rs75603675 TMPRSS2 and rs2227692 SERPINE1 polymorphisms are associated with a poor outcome. Additionally, rs2227692 SERPINE1 could participate in hypercoagulable conditions in critical COVID-19 patients, and this genetic variant could contribute to the identification of new pharmacological targets and treatment strategies to block the inhibition of TMPRSS2 entry into SARS-CoV-2.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The fatal contribution of serine protease-related genetic variants to COVID-19 outcomes

Martínez-Gómez,

Martinez-Armenta,

Tusie-Luna

et al. 2024

Front. Immunol.

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“…Furthermore, it eliminates the need for a predetermined selection of a specific genetic model. It is worth noting that this metric has been successfully applied in diverse research contexts, including studies related to conditions like diabetic nephropathy, IgAN, and chronic kidney disease [46][47][48][49][50][51][52].…”

Section: Discussionmentioning

confidence: 99%

Interleukin Variants Are Associated with the Development and Progression of IgA Nephropathy: A Candidate-Gene Association Study and Meta-Analysis

Chronopoulou,

Tziastoudi,

Pissas

et al. 2023

IJMS

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The interleukin-1 gene cluster encodes cytokines, which modulate mesangial cell proliferation and matrix expansion, both constituting central factors in the development and progression of immunoglobulin A nephropathy (IgAN). A candidate-gene study was performed to examine the association of polymorphisms of the interleukin-1 gene cluster with the risk of progressive IgAN. To gain deeper insights into the involvement of interleukin genes in IgAN, a meta-analysis of genetic association studies (GAS) that examine the association between interleukin variants and IgAN was conducted. Association study: The case-control study consisted of 121 unrelated Caucasians with sporadic, histologically diagnosed IgAN and of 246 age- and sex-matched healthy controls. Persistent proteinuria (>2 g/24 h) and/or impaired kidney function (serum creatinine > 1.5 mg/dL) defined progressive (n = 67) vs. non-progressive (n = 54) IgAN cases. Genotypes were assessed for two promoter-region single-nucleotide polymorphisms, C-899T (rs1800587) in IL1A and C-511T (rs16944) in IL1B, and for one penta-allelic variable-length tandem repeat polymorphism (VNTR 86 bp intron 2) in IL1RN. The association of these variants with the susceptibility of IgAN and the development of progressive IgAN (healthy status, IgAN, progressive IgAN) was tested using the generalized odds ratio (ORG) metric. Linkage disequilibrium and haplotype analysis were also performed. Meta-analysis: We included in the meta-analysis 15 studies investigating association between 14 interleukin variants harbored in eight different genes and IgAN. The ORG was used to evaluate the association between interleukin variants and IgAN using random effects models. The present case-control study revealed association of IL1B C-511T (rs16944) with the progression of IgAN (p = 0.041; ORG = 2.11 (1.09–4.07)). On haplotype analysis, significant results were derived for the haplotypes C-C-1 (p = 0.005; OR = 0.456 (0.261~0.797)) and C-T-2 (p = 0.003; OR = 4.208 (1.545–11.50)). Regarding association and meta-analysis results, variants in IL1B (rs1143627 and rs16944), IL1RN (rs928940, rs439154, and rs315951) and IL10 (rs1800871) were associated with IgAN based on either genotype or allele counts. Genetic variants and haplotypes in the IL1B, IL1RN, and IL10 genes might contribute to an increased risk for development and progression of IgAN.

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“…Given the undoubtedly genetic involvement in the course of DN, many genetic studies, such as linkage scans and genetic association studies (GAS), as well as meta-analyses of these studies, have been published [ 12 , 13 , 14 , 15 , 16 ]. A major contribution to the genetic dissection of DN has been made by genome-wide association studies (GWAS) and their meta-analyses [ 17 , 18 , 19 , 20 , 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

Key Genetic Components of Fibrosis in Diabetic Nephropathy: An Updated Systematic Review and Meta-Analysis

Tziastoudi

Nikolaou

et al. 2022

IJMS

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Renal fibrosis (RF) constitutes the common end-point of all kinds of chronic kidney disease (CKD), regardless of the initial cause of disease. The aim of the present study was to identify the key players of fibrosis in the context of diabetic nephropathy (DN). A systematic review and meta-analysis of all available genetic association studies regarding the genes that are included in signaling pathways related to RF were performed. The evaluated studies were published in English and they were included in PubMed and the GWAS Catalog. After an extensive literature review and search of the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, eight signaling pathways related to RF were selected and all available genetic association studies of these genes were meta-analyzed. ACE, AGT, EDN1, EPO, FLT4, GREM1, IL1B, IL6, IL10, IL12RB1, NOS3, TGFB1, IGF2/INS/TH cluster, and VEGFA were highlighted as the key genetic components driving the fibrosis process in DN. The present systematic review and meta-analysis indicate, as key players of fibrosis in DN, sixteen genes. However, the results should be interpreted with caution because the number of studies was relatively small.

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Serpin Family E Member 1 Tag Single-Nucleotide Polymorphisms in Patients with Diabetic Nephropathy: An Association Study and Meta-Analysis Using a Genetic Model-Free Approach

Cited by 6 publications

References 47 publications

The fatal contribution of serine protease-related genetic variants to COVID-19 outcomes

The fatal contribution of serine protease-related genetic variants to COVID-19 outcomes

Interleukin Variants Are Associated with the Development and Progression of IgA Nephropathy: A Candidate-Gene Association Study and Meta-Analysis

Key Genetic Components of Fibrosis in Diabetic Nephropathy: An Updated Systematic Review and Meta-Analysis

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