المؤلفون: Cantu, E, Suzuki, Y, Diamond, JM, Ellis, J, Tiwari, J, Beduhn, B, Nellen, JR, Shah, R, Meyer, NJ, Lederer, DJ, Kawut, SM, Palmer, SM, Snyder, LD, Hartwig, MG, Lama, VN, Bhorade, S, Crespo, M, Demissie, E, Wille, K, Orens, J, Shah, PD, Weinacker, A, Weill, D, Wilkes, D, Roe, D, Ware, LB, Wang, F, Feng, R, Christie, JD, Group, for the Lung Transplant Outcomes

المصدر: American Journal of Transplantation. 16(3)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Immunology, Clinical Research, Rare Diseases, Lung, Acute Respiratory Distress Syndrome, Genetics, Human Genome, Adult, Biomarkers, Female, Follow-Up Studies, Genetic Variation, Genotype, Humans, Intracellular Signaling Peptides and Proteins, Lung Transplantation, Male, Middle Aged, Phenotype, Plasminogen Activator Inhibitor 1, Primary Graft Dysfunction, Prognosis, Prospective Studies, Quantitative Trait Loci, translational research, science, lung transplantation, pulmonology, ischemia reperfusion injury, lung (allograft) function, dysfunction, lung disease, immune, inflammatory, Lung Transplant Outcomes Group, Medical and Health Sciences, Surgery, Clinical sciences

الوصف: The authors previously identified plasma plasminogen activator inhibitor-1 (PAI-1) level as a quantitative lung injury biomarker in primary graft dysfunction (PGD). They hypothesized that plasma levels of PAI-1 used as a quantitative trait could facilitate discovery of genetic loci important in PGD pathogenesis. A two-stage cohort study was performed. In stage 1, they tested associations of loci with PAI-1 plasma level using linear modeling. Genotyping was performed using the Illumina CVD Bead Chip v2. Loci meeting a p < 5 × 10(-4) cutoff were carried forward and tested in stage 2 for association with PGD. Two hundred ninety-seven enrollees were evaluated in stage 1. Six loci, associated with PAI-1, were carried forward to stage 2 and evaluated in 728 patients. rs3168046 (Toll interacting protein [TOLLIP]) was significantly associated with PGD (p = 0.006). The increased risk of PGD for carrying at least one copy of this variant was 11.7% (95% confidence interval 4.9-18.5%). The false-positive rate for individuals with this genotype who did not have PGD was 6.1%. Variants in the TOLLIP gene are associated with higher circulating PAI-1 plasma levels and validate for association with clinical PGD. A protein quantitative trait analysis for PGD risk prioritizes genetic variations in TOLLIP and supports a role for Toll-like receptors in PGD pathogenesis.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/5352n17hTest

المؤلفون: Cantu, E., Suzuki, Y., Diamond, J. M., Ellis, J., Tiwari, J., Beduhn, B., Nellen, J. R., Shah, R., Meyer, N. J., Lederer, D. J., Kawut, S. M., Palmer, S. M., Snyder, L. D., Hartwig, M. G., Lama, V. N., Bhorade, S., Crespo, M., Demissie, E., Wille, K., Orens, J., Shah, P. D., Weinacker, A., Weill, D., Wilkes, D., Roe, D., Ware, L. B., Wang, F., Feng, R., Christie, J. D.

مصطلحات موضوعية: lung disease, immune, inflammatory, lung (allograft) function, dysfunction, pulmonology, translational research, science, lung transplantation, ischemia reperfusion injury (IRI), Medicine (General), Health Sciences

الوصف: The authors previously identified plasma plasminogen activator inhibitor‐1 (PAI‐1) level as a quantitative lung injury biomarker in primary graft dysfunction (PGD). They hypothesized that plasma levels of PAI‐1 used as a quantitative trait could facilitate discovery of genetic loci important in PGD pathogenesis. A two‐stage cohort study was performed. In stage 1, they tested associations of loci with PAI‐1 plasma level using linear modeling. Genotyping was performed using the Illumina CVD Bead Chip v2. Loci meeting a p < 5 × 10−4 cutoff were carried forward and tested in stage 2 for association with PGD. Two hundred ninety‐seven enrollees were evaluated in stage 1. Six loci, associated with PAI‐1, were carried forward to stage 2 and evaluated in 728 patients. rs3168046 (Toll interacting protein [TOLLIP]) was significantly associated with PGD (p = 0.006). The increased risk of PGD for carrying at least one copy of this variant was 11.7% (95% confidence interval 4.9–18.5%). The false‐positive rate for individuals with this genotype who did not have PGD was 6.1%. Variants in the TOLLIP gene are associated with higher circulating PAI‐1 plasma levels and validate for association with clinical PGD. A protein quantitative trait analysis for PGD risk prioritizes genetic variations in TOLLIP and supports a role for Toll‐like receptors in PGD pathogenesis.Plasma plasminogen activator inhibitor‐1 quantitative trait analysis prioritizes genetic variations in TOLLIP for posttransplant primary graft dysfunction and supports a role for Toll‐like receptors in primary graft dysfunction pathogenesis. ; Peer Reviewed ; http://deepblue.lib.umich.edu/bitstream/2027.42/134189/1/ajt13525.pdfTest

وصف الملف: application/pdf

العلاقة: Cantu, E.; Suzuki, Y.; Diamond, J. M.; Ellis, J.; Tiwari, J.; Beduhn, B.; Nellen, J. R.; Shah, R.; Meyer, N. J.; Lederer, D. J.; Kawut, S. M.; Palmer, S. M.; Snyder, L. D.; Hartwig, M. G.; Lama, V. N.; Bhorade, S.; Crespo, M.; Demissie, E.; Wille, K.; Orens, J.; Shah, P. D.; Weinacker, A.; Weill, D.; Wilkes, D.; Roe, D.; Ware, L. B.; Wang, F.; Feng, R.; Christie, J. D. (2016). "Protein Quantitative Trait Loci Analysis Identifies Genetic Variation in the Innate Immune Regulator TOLLIP in Post–Lung Transplant Primary Graft Dysfunction Risk." American Journal of Transplantation (3): 833-840.; https://hdl.handle.net/2027.42/134189Test; American Journal of Transplantation; Christie JD, Kotloff RM, Ahya VN, et al. The effect of primary graft dysfunction on survival after lung transplantation. Am J Respir Crit Care Med 2005; 171: 1312 – 1316.; Lee JC, Christie JD, Keshavjee S. Primary graft dysfunction: Definition, risk factors, short‐ and long‐term outcomes. Semin Respir Crit Care Med 2010; 31: 161 – 171.; Klarstrom Engstrom K, Khalaf H, Kalvegren H, Bengtsson T. The role of Porphyromonas gingivalis gingipains in platelet activation and innate immune modulation. Mol Oral Microbiol 2015; 30: 62 – 73.; Shetty S, Padijnayayveetil J, Tucker T, et al. The fibrinolytic system and the regulation of lung epithelial cell proteolysis, signaling, and cellular viability. Am J Physiol Lung Cell Mol Physiol 2008; 295: L967 – l975.; Sapru A, Curley MA, Brady S, Matthay MA, Flori H. Elevated PAI‐1 is associated with poor clinical outcomes in pediatric patients with acute lung injury. Intensive Care Med 2010; 36: 157 – 163.; Diamond JM, Lederer DJ, Kawut SM, et al. Elevated plasma long pentraxin‐3 levels and primary graft dysfunction after lung transplantation for idiopathic pulmonary fibrosis. Am J Transplant 2011; 11: 2517 – 2522.; Shah JA, Vary JC, Chau TT, et al. Human TOLLIP regulates TLR2 and TLR4 signaling and its polymorphisms are associated with susceptibility to tuberculosis. J Immunol 2012; 189: 1737 – 1746.; Schimming TT, Parwez Q, Petrasch‐Parwez E, Nothnagel M, Epplen JT, Hoffjan S. Association of toll‐interacting protein gene polymorphisms with atopic dermatitis. BMC Dermatol 2007; 7: 3.; Steenholdt C, Andresen L, Pedersen G, Hansen A, Brynskov J. Expression and function of toll‐like receptor 8 and Tollip in colonic epithelial cells from patients with inflammatory bowel disease. Scand J Gastroenterol 2009; 44: 195 – 204.; Wang L, Jia P, Wolfinger RD, et al. Gene set analysis of genome‐wide association studies: Methodological issues and perspectives. Genomics 2011; 98: 1 – 8.; Daud SA, Yusen RD, Meyers BF, et al. Impact of immediate primary lung allograft dysfunction on bronchiolitis obliterans syndrome. Am J Respir Crit Care Med 2007; 175: 507 – 513.; Suzuki Y, Cantu E, Christie JD. Primary graft dysfunction. Semin Respir Crit Care Med 2013; 34: 305 – 319.; Yusen RD, Edwards LB, Kucheryavaya AY, et al. The Registry of the International Society for Heart and Lung Transplantation: Thirty‐First Adult Lung and Heart‐Lung Transplant Report—2014; Focus Theme: Retransplantation. J Heart Lung Transplant 2014; 33: 1009 – 1024.; Diamond JM, Lee JC, Kawut SM, et al. Clinical risk factors for primary graft dysfunction after lung transplantation. Am J Respir Crit Care Med 2013; 187: 527 – 534.; Katoh S, Honda S, Watanabe T, et al. Atrial endothelial impairment through Toll‐like receptor 4 signaling causes atrial thrombogenesis. Heart Vessels 2014; 29: 263 – 272.; Lo YL, Beckhouse AG, Boulus SL, Wells CA. Diversification of TOLLIP isoforms in mouse and man. Mamm Genome 2009; 20: 305 – 314.; Dowling JK, O’Neill LA. Biochemical regulation of the inflammasome. Crit Rev Biochem Mol Biol 2012; 47: 424 – 443.; Capelluto DG. Tollip: A multitasking protein in innate immunity and protein trafficking. Microbes Infect 2012; 14: 140 – 147.; Jeong E, Lee JY. Intrinsic and extrinsic regulation of innate immune receptors. Yonsei Med J 2011; 52: 379 – 392.; Cantu E, Lederer DJ, Meyer K, et al. Gene set enrichment analysis identifies key innate immune pathways in primary graft dysfunction after lung transplantation. Am J Transplant 2013; 13: 1898 – 1904.; Meyer NJ, Li M, Feng R, et al. ANGPT2 genetic variant is associated with trauma‐associated acute lung injury and altered plasma angiopoietin‐2 isoform ratio. Am J Respir Crit Care Med 2011; 183: 1344 – 1353.; Diamond JM, Meyer NJ, Feng R, et al. Variation in PTX3 is associated with primary graft dysfunction after lung transplantation. Am J Respir Crit Care Med 2012; 186: 546 – 552.; Diamond JM, Akimova T, Kazi A, et al. Genetic variation in the prostaglandin E2 pathway is associated with primary graft dysfunction. Am J Respir Crit Care Med 2014; 189: 567 – 575.; Noth I, Zhang Y, Ma SF, et al. Genetic variants associated with idiopathic pulmonary fibrosis susceptibility and mortality: A genome‐wide association study. Lancet Respir Med 2013; 1: 309 – 317.; Johnson AD, Handsaker RE, Pulit SL, Nizzari MM, O’Donnell CJ, de Bakker PI. SNAP: A web‐based tool for identification and annotation of proxy SNPs using HapMap. Bioinformatics 2008; 24: 2938 – 2939.; Carlson CS, Eberle MA, Rieder MJ, et al. Selecting a maximally informative set of single‐nucleotide polymorphisms for association analyses using linkage disequilibrium. Am J Hum Genet 2004; 74: 106 – 120.; Meyer NJ, Feng R, Li M, et al. IL1RN coding variant is associated with lower risk of acute respiratory distress syndrome and increased plasma IL‐1 receptor antagonist. Am J Respir Crit Care Med 2013; 187: 950 – 959.; Christie JD, Wurfel MM, Feng R, et al. Genome wide association identifies PPFIA1 as a candidate gene for acute lung injury risk following major trauma. PLoS One 2012; 7: e28268.; Price AL, Patterson NJ, Plenge RM, Weinblatt ME, Shadick NA, Reich D. Principal components analysis corrects for stratification in genome‐wide association studies. Nat Genet 2006; 38: 904 – 909.; Satagopan JM, Elston RC. Optimal two‐stage genotyping in population‐based association studies. Genet Epidemiol 2003; 25: 149 – 157.; Keating BJ, Tischfield S, Murray SS, et al. Concept, design and implementation of a cardiovascular gene‐centric 50 k SNP array for large‐scale genomic association studies. PLoS ONE 2008; 3: e3583.; Shah RJ, Diamond JM, Cantu E, et al. Latent class analysis identifies distinct phenotypes of primary graft dysfunction after lung transplantation. Chest 2013; 144: 616 – 622.; Ware LB, Matthay MA, Parsons PE, et al. Pathogenetic and prognostic significance of altered coagulation and fibrinolysis in acute lung injury/acute respiratory distress syndrome. Crit Care Med 2007; 35: 1821 – 1828.; Horrevoets AJ. Plasminogen activator inhibitor 1 (PAI‐1): In vitro activities and clinical relevance. Br J Haematol 2004; 125: 12 – 23.; Shah RJ, Bellamy SL, Localio AR, et al. A panel of lung injury biomarkers enhances the definition of primary graft dysfunction (PGD) after lung transplantation. J Heart Lung Transplant 2012; 31: 942 – 949.; Schliekelman P. Statistical power of expression quantitative trait loci for mapping of complex trait loci in natural populations. Genetics 2008; 178: 2201 – 2216.; Schadt EE, Monks SA, Drake TA, et al. Genetics of gene expression surveyed in maize, mouse and man. Nature 2003; 422: 297 – 302.

الإتاحة: https://doi.org/10.1111/ajt.13525Test
https://hdl.handle.net/2027.42/134189Test

المؤلفون: Cantu, E, Suzuki, Y, Diamond, JM, Ellis, J, Tiwari, J, Beduhn, B, Nellen, JR, Shah, R, Meyer, NJ, Lederer, DJ, Kawut, SM, Palmer, SM, Snyder, LD, Hartwig, MG, Lama, VN, Bhorade, S, Crespo, M, Demissie, E, Wille, K, Orens, J, Shah, PD, Weinacker, A, Weill, D, Wilkes, D, Roe, D, Ware, LB, Wang, F, Feng, R, Christie, JD, Lung Transplant Outcomes Group

المصدر: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, vol 16, iss 3

مصطلحات موضوعية: Adult, Male, lung disease, Genotype, Quantitative Trait Loci, inflammatory, Medical and Health Sciences, Lung Transplant Outcomes Group, Rare Diseases, Clinical Research, Plasminogen Activator Inhibitor 1, lung transplantation, Genetics, Humans, Prospective Studies, pulmonology, Acute Respiratory Distress Syndrome, Lung, science, ischemia reperfusion injury, dysfunction, Human Genome, Intracellular Signaling Peptides and Proteins, Genetic Variation, Middle Aged, Prognosis, lung (allograft) function, Phenotype, translational research, Female, Surgery, Primary Graft Dysfunction, immune, Biomarkers, Follow-Up Studies

الوصف: The authors previously identified plasma plasminogen activator inhibitor-1 (PAI-1) level as a quantitative lung injury biomarker in primary graft dysfunction (PGD). They hypothesized that plasma levels of PAI-1 used as a quantitative trait could facilitate discovery of genetic loci important in PGD pathogenesis. A two-stage cohort study was performed. In stage 1, they tested associations of loci with PAI-1 plasma level using linear modeling. Genotyping was performed using the Illumina CVD Bead Chip v2. Loci meeting a p < 5 × 10(-4) cutoff were carried forward and tested in stage 2 for association with PGD. Two hundred ninety-seven enrollees were evaluated in stage 1. Six loci, associated with PAI-1, were carried forward to stage 2 and evaluated in 728 patients. rs3168046 (Toll interacting protein [TOLLIP]) was significantly associated with PGD (p = 0.006). The increased risk of PGD for carrying at least one copy of this variant was 11.7% (95% confidence interval 4.9-18.5%). The false-positive rate for individuals with this genotype who did not have PGD was 6.1%. Variants in the TOLLIP gene are associated with higher circulating PAI-1 plasma levels and validate for association with clinical PGD. A protein quantitative trait analysis for PGD risk prioritizes genetic variations in TOLLIP and supports a role for Toll-like receptors in PGD pathogenesis.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=od_______325::bb8bc18d65b7697ac3bccc0db8a06c75Test
https://escholarship.org/uc/item/5352n17hTest