Variation in PTX3 Is Associated with Primary Graft Dysfunction after Lung Transplantation

Elevated long pentraxin-3 (PTX3) levels are associated with the development of primary graft dysfunction (PGD) after lung transplantation. Abnormalities in innate immunity, mediated by PTX3 release, may play a role in PGD pathogenesis. Our goal was to test whether variants in the gene encoding PTX3...

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Published in:	American journal of respiratory and critical care medicine Vol. 186; no. 6; pp. 546 - 552
Main Authors:	DIAMOND, Joshua M, MEYER, Nuala J, BHORADE, Sangeeta, CRESPO, Maria, DEMISSIE, Ejigayehu, SONETT, Joshua, WILLE, Keith, ORENS, Jonathan, WEINACKER, Ann, WEILL, David, ARCASOY, Selim, SHAH, Pali D, FENG, Rui, BELPERIO, John A, WILES, David, WARE, Lorraine B, PALMER, Scott M, CHRISTIE, Jason D, RUSHEFSKI, Melanie, LEDERER, David J, KAWUT, Steven M, LEE, James C, CANTU, Edward, SHAHE, Rupal J, LAMA, Vibha N
Format:	Journal Article
Language:	English
Published:	New York, NY American Thoracic Society 15-09-2012
Subjects:	Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Biological and medical sciences Bone marrow, stem cells transplantation. Graft versus host reaction C-Reactive Protein - genetics C-Reactive Protein - metabolism Cohort Studies Confidence Intervals Female Follow-Up Studies Genetic Association Studies Genotype Graft Rejection - epidemiology Graft Rejection - genetics Graft Survival Haplotypes Health risk assessment Humans Idiopathic Pulmonary Fibrosis - diagnosis Idiopathic Pulmonary Fibrosis - surgery Incidence Intensive care medicine Ischemia Logistic Models Lung diseases Lung Transplantation - adverse effects Lung Transplantation - methods Lung transplants Male Medical sciences Middle Aged Odds Ratio Patients Plasma Polymorphism, Single Nucleotide Primary Graft Dysfunction - genetics Primary Graft Dysfunction - pathology Pulmonary Disease, Chronic Obstructive - diagnosis Pulmonary Disease, Chronic Obstructive - surgery Pulmonary fibrosis Regression analysis Retrospective Studies Risk Assessment Serum Amyloid P-Component - genetics Serum Amyloid P-Component - metabolism Severity of Illness Index Statistical analysis Statistics, Nonparametric Time Factors Transfusions. Complications. Transfusion reactions. Cell and gene therapy Intensive care long pentraxin 3 lung transplantation Single nucleotide polymorphism Graft primary dysfunction single-nucleotide polymorphism Resuscitation primary graft dysfunction
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Summary:	Elevated long pentraxin-3 (PTX3) levels are associated with the development of primary graft dysfunction (PGD) after lung transplantation. Abnormalities in innate immunity, mediated by PTX3 release, may play a role in PGD pathogenesis. Our goal was to test whether variants in the gene encoding PTX3 are risk factors for PGD. We performed a candidate gene association study in recipients from the multicenter, prospective Lung Transplant Outcomes Group cohort enrolled between July 2002 and July 2009. The primary outcome was International Society for Heart and Lung Transplantation grade 3 PGD within 72 hours of transplantation. Targeted genotyping of 10 haplotype-tagging PTX3 single-nucleotide polymorphisms (SNPs) was performed in lung transplant recipients. The association between PGD and each SNP was evaluated by logistic regression, adjusting for pretransplantation lung disease, cardiopulmonary bypass use, and population stratification. The association between SNPs and plasma PTX3 levels was tested across genotypes in a subset of recipients with idiopathic pulmonary fibrosis. Six hundred fifty-four lung transplant recipients were included. The incidence of PGD was 29%. Two linked 5' region variants, rs2120243 and rs2305619, were associated with PGD (odds ratio, 1.5; 95% confidence interval, 1.1 to 1.9; P = 0.006 and odds ratio, 1.4; 95% confidence interval, 1.1 to 1.9; P = 0.007, respectively). The minor allele of rs2305619 was significantly associated with higher plasma PTX3 levels measured pretransplantation (P = 0.014) and at 24 hours (P = 0.047) after transplantation in patients with idiopathic pulmonary fibrosis. Genetic variants of PTX3 are associated with PGD after lung transplantation, and are associated with increased PTX3 plasma levels.
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ISSN:	1073-449X 1535-4970
DOI:	10.1164/rccm.201204-0692OC