scholarly journals Potential clinical utility of MUC5B und TOLLIP single nucleotide polymorphisms (SNPs) in the management of patients with IPF

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Francesco Bonella ◽  
Ilaria Campo ◽  
Michele Zorzetto ◽  
Eda Boerner ◽  
Shinichiro Ohshimo ◽  
...  
Keyword(s):  
Disease Progression ◽  
Clinical Utility ◽  
Minor Allele ◽  
Genotype Distribution ◽  
Nucleotide Polymorphisms ◽  
Chromosome 11 ◽  
Single Nucleotide ◽  
Rapid Disease Progression ◽  
Potential Clinical Utility ◽  
One Year

Abstract Background Genetic variants of TOLLIP and MUC5B, both on chromosome 11, have been reported to be associated with the development and/or prognosis of idiopathic pulmonary fibrosis (IPF). This retrospective study was conducted to investigate the association of MUC5B and TOLLIP SNPs with disease outcome in IPF. 62 IPF patients and 50 healthy controls (HC) from our Institution were genotyped for SNPs within MUC5B (rs35705950) and TOLLIP (rs3750920 and rs5743890). Correlation of SNPs genotypes with survival, acute exacerbation (AE) or disease progression (defined as a decline of ≥ 5% in FVC and or ≥ 10% in DLco in one year) was investigated. Results The MUC5B rs35705950 minor allele (T) was more frequent in IPF subjects than in HC (35% vs 9% p < 0.001). TOLLIP SNPs alleles and genotype distribution did not differ between IPF and HC and did not vary according to gender, age, BMI and lung functional impairment at baseline. The minor allele (C) in TOLLIP rs5743890 was associated with worse survival and with disease progression in all performed analyses. The MUC5B rs35705950 or the TOLLIP rs3750920 minor allele, were not associated with disease progression or AE. Conclusion We confirm that the minor allele of MUC5B rs35705950 is associated with IPF. The minor allele of TOLLIP rs5743890 appears to be a predictor of worse survival and more rapid disease progression, therefore being of potential utility to stratify IPF patients at baseline.

scholarly journals Potential Clinical Utility of MUC5B und TOLLIP Single Nucleotide Polymorphisms (SNPs) in the Management of Patients with IPF

2020 ◽  
Author(s):  
Francesco Bonella ◽  
Ilaria Campo ◽  
Michele Zorzetto ◽  
Eda Börner ◽  
Shinichiro Ohshimo ◽  
...  
Keyword(s):  
Disease Progression ◽  
Acute Exacerbation ◽  
Minor Allele ◽  
Genotype Distribution ◽  
Nucleotide Polymorphisms ◽  
Chromosome 11 ◽  
Single Nucleotide ◽  
Rapid Disease Progression ◽  
Potential Clinical Utility ◽  
One Year

Abstract Background: Genetic variants of TOLLIP and MUC5B, both on chromosome 11, have been reported to be associated with the development and/or prognosis of idiopathic pulmonary fibrosis (IPF). This retrospective study was conducted to investigate the association of MUC5B and TOLLIP SNPs with disease outcome in IPF. 62 IPF patients and 50 healthy controls (HC) from our Institution were genotyped for SNPs within MUC5B (rs35705950) and TOLLIP (rs3750920 and rs5743890). Correlation of SNPs genotypes with survival, acute exacerbation (AE) or disease progression (defined as a decline of ≥ 5% in FVC and or >10% in DLco in one year) was investigated.Results: The MUC5B rs35705950 minor allele (T) was more frequent in IPF subjects than in HC (35% vs 9% p<0.001). TOLLIP SNPs alleles and genotype distribution did not differ between IPF and HC and did not vary according to gender, age, BMI and lung functional impairment at baseline. The minor allele (C) in TOLLIP rs5743890 was associated with worse survival and with disease progression in all performed analyses. The MUC5B rs35705950 or the TOLLIP rs3750920 minor allele, were not associated with disease progression or acute exacerbation. Conclusion: We confirm that the minor allele of MUC5B rs35705950 is associated with IPF. The minor allele of TOLLIP rs5743890 appears to be a predictor of worse survival and more rapid disease progression, therefore being of potential utility to stratify IPF patients at baseline.

scholarly journals Potential clinical utility of MUC5B und TOLLIP single nucleotide polymorphisms (SNPs) in the management of patients with IPF

2021 ◽  
Author(s):  
F. Bonella ◽  
Ilaria Campo ◽  
Michele Zorzetto ◽  
Eda Börner ◽  
Shinichiro Ohshimo ◽  
...  
Keyword(s):  
Disease Progression ◽  
Acute Exacerbation ◽  
Minor Allele ◽  
Genotype Distribution ◽  
Nucleotide Polymorphisms ◽  
Chromosome 11 ◽  
Single Nucleotide ◽  
Rapid Disease Progression ◽  
Potential Clinical Utility ◽  
One Year

Abstract Background: Genetic variants of TOLLIP and MUC5B, both on chromosome 11, have been reported to be associated with the development and/or prognosis of idiopathic pulmonary fibrosis (IPF). This retrospective study was conducted to investigate the association of MUC5B and TOLLIP SNPs with disease outcome in IPF. 62 IPF patients and 50 healthy controls (HC) from our Institution were genotyped for SNPs within MUC5B (rs35705950) and TOLLIP (rs3750920 and rs5743890). Correlation of SNPs genotypes with survival, acute exacerbation (AE) or disease progression (defined as a decline of ≥ 5% in FVC and or >10% in DLco in one year) was investigated.Results: The MUC5B rs35705950 minor allele (T) was more frequent in IPF subjects than in HC (35% vs 9% p<0.001). TOLLIP SNPs alleles and genotype distribution did not differ between IPF and HC and did not vary according to gender, age, BMI and lung functional impairment at baseline. The minor allele (C) in TOLLIP rs5743890 was associated with worse survival and with disease progression in all performed analyses. The MUC5B rs35705950 or the TOLLIP rs3750920 minor allele, were not associated with disease progression or acute exacerbation. Conclusion: We confirm that the minor allele of MUC5B rs35705950 is associated with IPF. The minor allele of TOLLIP rs5743890 appears to be a predictor of worse survival and more rapid disease progression, therefore being of potential utility to stratify IPF patients at baseline.

scholarly journals Human TERT promoter mutations as a prognostic biomarker in glioma

2021 ◽  
Vol 147 (4) ◽  
pp. 1007-1017
Author(s):  
Branka Powter ◽  
Sarah A. Jeffreys ◽  
Heena Sareen ◽  
Adam Cooper ◽  
Daniel Brungs ◽  
...  
Keyword(s):  
Clinical Utility ◽  
Nucleotide Polymorphism ◽  
Liquid Biopsies ◽  
Single Nucleotide ◽  
Tert Promoter ◽  
Tert Promoter Mutations ◽  
Potential Clinical Utility ◽  
Promoter Mutations ◽  
The Relationship ◽  
Potential Use

AbstractThe TERT promoter (pTERT) mutations, C228T and C250T, play a significant role in malignant transformation by telomerase activation, oncogenesis and immortalisation of cells. C228T and C250T are emerging as important biomarkers in many cancers including glioblastoma multiforme (GBM), where the prevalence of these mutations is as high as 80%. Additionally, the rs2853669 single nucleotide polymorphism (SNP) may cooperate with these pTERT mutations in modulating progression and overall survival in GBM. Using liquid biopsies, pTERT mutations, C228T and C250T, and other clinically relevant biomarkers can be easily detected with high precision and sensitivity, facilitating longitudinal analysis throughout therapy and aid in cancer patient management.In this review, we explore the potential for pTERT mutation analysis, via liquid biopsy, for its potential use in personalised cancer therapy. We evaluate the relationship between pTERT mutations and other biomarkers as well as their potential clinical utility in early detection, prognostication, monitoring of cancer progress, with the main focus being on brain cancer.

scholarly journals 173 The role of an intronic single nucleotide polymorphism within the dopamine receptor type-2 gene on pituitary prolactin protein expression in bulls

2020 ◽  
Vol 98 (Supplement_2) ◽  
pp. 37-37
Author(s):  
Andrea N DeCarlo ◽  
Keelee J McCarty ◽  
Sarah K Richey ◽  
Nathan Long ◽  
Scott Pratt
Keyword(s):  
Protein Expression ◽  
Genotype Distribution ◽  
Nucleotide Polymorphisms ◽  
Genotypic Effect ◽  
Single Nucleotide ◽  
Detection Range ◽  
Cull Cows ◽  
Densitometry Analysis ◽  
Pcr Products

Abstract Detrimental effects to male reproductive physiology have been observed due to changes in prolactin (PRL) serum concentration. Regulation of PRL by dopamine binding to the dopamine type-2 receptor (DRD2) is well defined and associations between male physiology and single nucleotide polymorphisms (SNPs) within the DRD2 gene have been observed. The objective of the study was to evaluate association of a DRD2 SNP to PRL protein expression in bulls. Testis and epididymis were collected from bulls grazing a forage containing or lacking a dopamine agonist at the end of a 126 d study (n = 14). Bovine pituitaries (n = 587) were collected randomly over 3 mo from a local abattoir which processes cull cows and bulls. Sex of pituitaries was verified (n = 259 males) by duplex PCR for amplification of SRY and b-actin followed by Southern blotting of PCR products for selection of male. Prolactin protein expression was assessed in testis, epididymis, and pituitary by western blotting. Expression of PRL protein was below detection range in reproductive tissues but was present in pituitary, therefore experiments continued in pituitary. Restriction fragment length polymorphism genotyping was performed on pituitaries by amplification of the DRD2 SNP region followed by digestion with a Tfil enzyme. Digested of products produced 3,2, or 1 band (AG, AA, GG, respectively). A subset of male pituitaries was blotted by slot blot manifold and PRL protein expression assessed by immunodetection and densitometry analysis normalized to GAPDH expression. Pituitary genotype distribution was 17.4% AA (n = 16), 63% AG (n = 58), and 19.6% GG (n = 18). Prolactin protein expression in the pituitary was similar across genotype (P = 0.23). These findings indicate that the DRD2 SNP has no genotypic effect on PRL protein expression in bovine pituitary.

Abstract 14359: Single Nucleotide Polymorphisms in Genes Involved in L-arginine / Dimethylarginine Metabolism Predispose for Pulmonary Hypertension and Acute Mountain Sickness at High Altitude

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Juliane Hannemann ◽  
Julia Zummack ◽  
PATRICIA SIQUES ◽  
JULIO BRITO ◽  
Rainer Boeger
Keyword(s):  
Pulmonary Hypertension ◽  
Relative Risk ◽  
Genetic Variability ◽  
High Altitude ◽  
Acute Mountain Sickness ◽  
Minor Allele ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Mountain Sickness ◽  
Study Participants

Introduction: Chronic (CH) and chronic-intermittent (CIH) exposure to hypoxia at high altitude causes acute or chronic mountain sickness and elevation of mean pulmonary arterial pressure (mPAP). This is paralleled by increased plasma levels of ADMA, an endogenous inhibitor of NO synthesis. ADMA is cleaved by dimethylarginine dimethylaminohydrolase (DDAH1 and DDAH2), whilst symmetric dimethylarginine (SDMA) is cleaved by AGXT2. Arginase (ARG1 and ARG2) competes with endothelial NO synthase (NOS3) for L-arginine as substrate. We have shown previously that baseline ADMA (at sea level) determines mPAP after six months of CIH; cut-off values of 25 mm Hg and 30 mm Hg are being used to diagnose high altitude pulmonary hypertension. Hypothesis: We hypothesized that genetic variability in genes coding for core enzymes of ADMA, SDMA, and L-arginine metabolism may predispose individuals for high altitude disease and pulmonary hypertension. Methods: We genotyped 16 common single nucleotide polymorphisms in the NOS3, DDAH1, DDAH2, AGXT2, ARG1 and ARG2 genes of 69 healthy male Chilean subjects. Study participants adhered to a CIH regimen (5d at 3,550m, 2d at sea level) for six months. Metabolites were measured by LC-MS/MS; mPAP was estimated by echocardiography at six months, and altitude acclimatization was assessed by Lake Louise Score and arterial oxygen saturation. Results: Carriers of the minor allele of DDAH1 rs233112 had a higher mean baseline ADMA level (0.76±0.03 vs. 0.67±0.02 μmol/l; p<0.05), whilst the major allele of DDAH2 rs805304 was linked to an exacerbated increase of ADMA in hypoxia (0.10±0.03 vs. 0.04±0.04 μmol/l; p<0.02). Study participants carrying the minor allele of ARG1 rs2781667 had a relative risk of elevated mPAP (>25 mm Hg) of 1.70 (1.56-1.85; p<0.0001), and carriers of the minor allele of NOS3 rs2070744 had a relative risk of elevated mPAP (>30 mm Hg) of 1.58 (1.47-1.69; p<0.0001). The NOS3 and DDAH2 genes were associated with the incidence of acute mountain sickness. Conclusions: We conclude that genetic variability in the L-arginine / ADMA / NO pathway is an important determinant of high altitude pulmonary hypertension and acute mountain sickness. DDAH1 is linked to baseline ADMA, whilst DDAH2 determines the response of ADMA to hypoxia.

scholarly journals Association Between Apical Periodontitis and TNF-α -308 G>A Gene Polymorphism: A Systematic Review and Meta-Analysis

2017 ◽  
Vol 28 (5) ◽  
pp. 535-542 ◽  
Author(s):  
Alessandro Guimarães Salles ◽  
Lívia Azeredo Alves Antunes ◽  
Patrícia Arriaga Carvalho ◽  
Erika Calvano Küchler ◽  
Leonardo Santos Antunes
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Apical Periodontitis ◽  
Permanent Teeth ◽  
Genotype Distribution ◽  
Nucleotide Polymorphisms ◽  
Eligibility Criteria ◽  
Single Nucleotide ◽  
Mesh Terms ◽  
Tnf Α

Abstract Currently, investigations have focused on the identification of Single Nucleotide Polymorphisms (SNP) involved in host response and its ability to generate an immunity deficiency. The aim of this study was to perform a systematic review (SR) and meta-analysis to evaluate the association between TNF-α -308 G>A polymorphism and apical periodontitis (AP) phenotypes. A broad search for studies was conducted. The following databases were used: PubMed, Scopus, Web of Science, and VHL (Medline, SciELO, Ibecs, and Lilacs). The MeSH terms “Periapical Periodontitis,” “Periapical Abscess,” “Polymorphism, Genetic,” and “Polymorphism, Single Nucleotide” were used. MeSH synonyms, related terms, and free terms were included. Clinical investigations of individuals with different AP phenotypes in permanent teeth were selected. After application of the eligibility criteria, selected studies were qualified by assessing their methodological quality. A fixed effect model was used for the meta-analysis. The initial search identified 71 references. After excluding duplicate abstracts, 33 were selected. From these, two were eligible for quality assessment and were classified as being of moderate evidence. The included studies did not demonstrate association between AP and TNF-α -308 G>A SNP. However, the meta-analysis demonstrated an association between the genotype distribution and AP phenotype (OR= 0.49; confidence interval= 0.25, 0.96; p=0.04). The role of TNF-α -308 G>A SNP in AP phenotypes is debatable. Further studies are needed to confirm and understand the underlying mechanisms of the identified association.

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