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, 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