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Variation in PTX3 is associated with primary graft dysfunction after lung transplantation.

Publication ,  Journal Article
Diamond, JM; Meyer, NJ; Feng, R; Rushefski, M; Lederer, DJ; Kawut, SM; Lee, JC; Cantu, E; Shah, RJ; Lama, VN; Bhorade, S; Crespo, M; Wille, K ...
Published in: Am J Respir Crit Care Med
September 15, 2012

RATIONALE: 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. OBJECTIVES: Our goal was to test whether variants in the gene encoding PTX3 are risk factors for PGD. METHODS: 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. MEASUREMENTS AND MAIN RESULTS: 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. CONCLUSIONS: Genetic variants of PTX3 are associated with PGD after lung transplantation, and are associated with increased PTX3 plasma levels.

Duke Scholars

Published In

Am J Respir Crit Care Med

DOI

EISSN

1535-4970

Publication Date

September 15, 2012

Volume

186

Issue

6

Start / End Page

546 / 552

Location

United States

Related Subject Headings

  • Time Factors
  • Statistics, Nonparametric
  • Severity of Illness Index
  • Serum Amyloid P-Component
  • Risk Assessment
  • Retrospective Studies
  • Respiratory System
  • Pulmonary Disease, Chronic Obstructive
  • Primary Graft Dysfunction
  • Polymorphism, Single Nucleotide
 

Citation

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Diamond, J. M., Meyer, N. J., Feng, R., Rushefski, M., Lederer, D. J., Kawut, S. M., … Lung Transplant Outcomes Group. (2012). Variation in PTX3 is associated with primary graft dysfunction after lung transplantation. Am J Respir Crit Care Med, 186(6), 546–552. https://doi.org/10.1164/rccm.201204-0692OC
Diamond, Joshua M., Nuala J. Meyer, Rui Feng, Melanie Rushefski, David J. Lederer, Steven M. Kawut, James C. Lee, et al. “Variation in PTX3 is associated with primary graft dysfunction after lung transplantation.Am J Respir Crit Care Med 186, no. 6 (September 15, 2012): 546–52. https://doi.org/10.1164/rccm.201204-0692OC.
Diamond JM, Meyer NJ, Feng R, Rushefski M, Lederer DJ, Kawut SM, et al. Variation in PTX3 is associated with primary graft dysfunction after lung transplantation. Am J Respir Crit Care Med. 2012 Sep 15;186(6):546–52.
Diamond, Joshua M., et al. “Variation in PTX3 is associated with primary graft dysfunction after lung transplantation.Am J Respir Crit Care Med, vol. 186, no. 6, Sept. 2012, pp. 546–52. Pubmed, doi:10.1164/rccm.201204-0692OC.
Diamond JM, Meyer NJ, Feng R, Rushefski M, Lederer DJ, Kawut SM, Lee JC, Cantu E, Shah RJ, Lama VN, Bhorade S, Crespo M, Demissie E, Sonett J, Wille K, Orens J, Weinacker A, Weill D, Arcasoy S, Shah PD, Belperio JA, Wilkes D, Ware LB, Palmer SM, Christie JD, Lung Transplant Outcomes Group. Variation in PTX3 is associated with primary graft dysfunction after lung transplantation. Am J Respir Crit Care Med. 2012 Sep 15;186(6):546–552.

Published In

Am J Respir Crit Care Med

DOI

EISSN

1535-4970

Publication Date

September 15, 2012

Volume

186

Issue

6

Start / End Page

546 / 552

Location

United States

Related Subject Headings

  • Time Factors
  • Statistics, Nonparametric
  • Severity of Illness Index
  • Serum Amyloid P-Component
  • Risk Assessment
  • Retrospective Studies
  • Respiratory System
  • Pulmonary Disease, Chronic Obstructive
  • Primary Graft Dysfunction
  • Polymorphism, Single Nucleotide