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

Joshua M. Diamond, Nuala J. Meyer, Rui Feng, Melanie Rushefski, David J. Lederer, Steven M. Kawut, James C. Lee, Edward Cantu, Rupal J. Shah, Vibha N. Lama, Sangeeta Bhorade, Maria Crespo, Ejigayehu Demissie, Joshua Sonett, Keith Wille, Jonathan B Orens, Ann Weinacker, David Weill, Selim Arcasoy, Pali Dedhiya ShahJohn A. Belperio, David Wilkes, Lorraine B. Ware, Scott M. Palmer, Jason D. Christie

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)546-552
Number of pages7
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume186
Issue number6
DOIs
StatePublished - Sep 15 2012

Fingerprint

Primary Graft Dysfunction
Lung Transplantation
Single Nucleotide Polymorphism
Idiopathic Pulmonary Fibrosis
Lung
Transplantation
Odds Ratio
Confidence Intervals
PTX3 protein
Genetic Association Studies
Cardiopulmonary Bypass
Innate Immunity
Haplotypes
Lung Diseases
Logistic Models
Alleles
Genotype
Transplants

Keywords

  • Long pentraxin 3
  • Lung transplantation
  • Primary graft dysfunction
  • Single-nucleotide polymorphism

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Diamond, J. M., Meyer, N. J., Feng, R., Rushefski, M., Lederer, D. J., Kawut, S. M., ... Christie, J. D. (2012). Variation in PTX3 is associated with primary graft dysfunction after lung transplantation. American Journal of Respiratory and Critical Care Medicine, 186(6), 546-552. https://doi.org/10.1164/rccm.201204-0692OC

Variation in PTX3 is associated with primary graft dysfunction after lung transplantation. / Diamond, Joshua M.; Meyer, Nuala J.; Feng, Rui; Rushefski, Melanie; Lederer, David J.; Kawut, Steven M.; Lee, James C.; Cantu, Edward; Shah, Rupal J.; Lama, Vibha N.; Bhorade, Sangeeta; Crespo, Maria; Demissie, Ejigayehu; Sonett, Joshua; Wille, Keith; Orens, Jonathan B; Weinacker, Ann; Weill, David; Arcasoy, Selim; Shah, Pali Dedhiya; Belperio, John A.; Wilkes, David; Ware, Lorraine B.; Palmer, Scott M.; Christie, Jason D.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 186, No. 6, 15.09.2012, p. 546-552.

Research output: Contribution to journalArticle

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, JB, Weinacker, A, Weill, D, Arcasoy, S, Shah, PD, Belperio, JA, Wilkes, D, Ware, LB, Palmer, SM & Christie, JD 2012, 'Variation in PTX3 is associated with primary graft dysfunction after lung transplantation', American Journal of Respiratory and Critical Care Medicine, vol. 186, no. 6, pp. 546-552. https://doi.org/10.1164/rccm.201204-0692OC
Diamond, Joshua M. ; Meyer, Nuala J. ; Feng, Rui ; Rushefski, Melanie ; Lederer, David J. ; Kawut, Steven M. ; Lee, James C. ; Cantu, Edward ; Shah, Rupal J. ; Lama, Vibha N. ; Bhorade, Sangeeta ; Crespo, Maria ; Demissie, Ejigayehu ; Sonett, Joshua ; Wille, Keith ; Orens, Jonathan B ; Weinacker, Ann ; Weill, David ; Arcasoy, Selim ; Shah, Pali Dedhiya ; Belperio, John A. ; Wilkes, David ; Ware, Lorraine B. ; Palmer, Scott M. ; Christie, Jason D. / Variation in PTX3 is associated with primary graft dysfunction after lung transplantation. In: American Journal of Respiratory and Critical Care Medicine. 2012 ; Vol. 186, No. 6. pp. 546-552.
@article{9af18984ac6f4114aee1962cfacaa103,
title = "Variation in PTX3 is associated with primary graft dysfunction after lung transplantation",
abstract = "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.",
keywords = "Long pentraxin 3, Lung transplantation, Primary graft dysfunction, Single-nucleotide polymorphism",
author = "Diamond, {Joshua M.} and Meyer, {Nuala J.} and Rui Feng and Melanie Rushefski and Lederer, {David J.} and Kawut, {Steven M.} and Lee, {James C.} and Edward Cantu and Shah, {Rupal J.} and Lama, {Vibha N.} and Sangeeta Bhorade and Maria Crespo and Ejigayehu Demissie and Joshua Sonett and Keith Wille and Orens, {Jonathan B} and Ann Weinacker and David Weill and Selim Arcasoy and Shah, {Pali Dedhiya} and Belperio, {John A.} and David Wilkes and Ware, {Lorraine B.} and Palmer, {Scott M.} and Christie, {Jason D.}",
year = "2012",
month = "9",
day = "15",
doi = "10.1164/rccm.201204-0692OC",
language = "English (US)",
volume = "186",
pages = "546--552",
journal = "American Journal of Respiratory and Critical Care Medicine",
issn = "1073-449X",
publisher = "American Thoracic Society",
number = "6",

}

TY - JOUR

T1 - Variation in PTX3 is associated with primary graft dysfunction after lung transplantation

AU - Diamond, Joshua M.

AU - Meyer, Nuala J.

AU - Feng, Rui

AU - Rushefski, Melanie

AU - Lederer, David J.

AU - Kawut, Steven M.

AU - Lee, James C.

AU - Cantu, Edward

AU - Shah, Rupal J.

AU - Lama, Vibha N.

AU - Bhorade, Sangeeta

AU - Crespo, Maria

AU - Demissie, Ejigayehu

AU - Sonett, Joshua

AU - Wille, Keith

AU - Orens, Jonathan B

AU - Weinacker, Ann

AU - Weill, David

AU - Arcasoy, Selim

AU - Shah, Pali Dedhiya

AU - Belperio, John A.

AU - Wilkes, David

AU - Ware, Lorraine B.

AU - Palmer, Scott M.

AU - Christie, Jason D.

PY - 2012/9/15

Y1 - 2012/9/15

N2 - 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.

AB - 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.

KW - Long pentraxin 3

KW - Lung transplantation

KW - Primary graft dysfunction

KW - Single-nucleotide polymorphism

UR - http://www.scopus.com/inward/record.url?scp=84866406579&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84866406579&partnerID=8YFLogxK

U2 - 10.1164/rccm.201204-0692OC

DO - 10.1164/rccm.201204-0692OC

M3 - Article

C2 - 22822025

AN - SCOPUS:84866406579

VL - 186

SP - 546

EP - 552

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

SN - 1073-449X

IS - 6

ER -