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.

• Authors: 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 Orens, Ann Weinacker, David Weill, Selim Arcasoy, Pali D Shah, John A Belperio, David Wilkes, Lorraine B Ware, Scott M Palmer, Jason D Christie, Lung Transplant Outcomes Group
• Journal: American journal of respiratory and critical care medicine (Am J Respir Crit Care Med) Vol. 186 Issue 6 Pg. 546-52 (Sep 15 2012) ISSN: 1535-4970 [Electronic] United States
• PMID: 22822025 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Serum Amyloid P-Component
• PTX3 protein
• C-Reactive Protein

Topics

• C-Reactive Protein (genetics, metabolism)
• Cohort Studies
• Confidence Intervals
• Female
• Follow-Up Studies
• Genetic Association Studies
• Genotype
• Graft Rejection (epidemiology, genetics)
• Graft Survival
• Haplotypes
• Humans
• Idiopathic Pulmonary Fibrosis (diagnosis, surgery)
• Incidence
• Logistic Models
• Lung Transplantation (adverse effects, methods)
• Male
• Middle Aged
• Odds Ratio
• Polymorphism, Single Nucleotide
• Primary Graft Dysfunction (genetics, pathology)
• Pulmonary Disease, Chronic Obstructive (diagnosis, surgery)
• Retrospective Studies
• Risk Assessment
• Serum Amyloid P-Component (genetics, metabolism)
• Severity of Illness Index
• Statistics, Nonparametric
• Time Factors