Dataset Information

Genetic risk factors for portopulmonary hypertension in patients with advanced liver disease.

ABSTRACT: Portopulmonary hypertension (PPHTN) occurs in 6% of liver transplant candidates. The pathogenesis of this complication of portal hypertension is poorly understood.To identify genetic risk factors for PPHTN in patients with advanced liver disease.We performed a multicenter case-control study of patients with portal hypertension. Cases had a mean pulmonary artery pressure >25 mm Hg, pulmonary vascular resistance >240 dynes.s(-1).cm(-5), and pulmonary capillary wedge pressure < or =15 mm Hg. Controls had a right ventricular systolic pressure < 40 mm Hg (if estimated) and normal right-sided cardiac morphology by transthoracic echocardiography. We genotyped 1,079 common single nucleotide polymorphisms (SNPs) in 93 candidate genes in each patient.The study sample included 31 cases and 104 controls. Twenty-nine SNPs in 15 candidate genes were associated with the risk of PPHTN (P < 0.05). Multiple SNPs in the genes coding for estrogen receptor 1, aromatase, phosphodiesterase 5, angiopoietin 1, and calcium binding protein A4 were associated with the risk of PPHTN. The biological relevance of one of the aromatase SNPs was supported by an association with plasma estradiol levels.Genetic variation in estrogen signaling and cell growth regulators is associated with the risk of PPHTN. These biologic pathways may elucidate the mechanism for the development of PPHTN in certain patients with severe liver disease.

SUBMITTER: Roberts KE

PROVIDER: S-EPMC2675568 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genetic risk factors for portopulmonary hypertension in patients with advanced liver disease.

Roberts Kari E KE Fallon Michael B MB Krowka Michael J MJ Brown Robert S RS Trotter James F JF Peter Inga I Tighiouart Hocine H Knowles James A JA Rabinowitz Daniel D Benza Raymond L RL Badesch David B DB Taichman Darren B DB Horn Evelyn M EM Zacks Steven S Kaplowitz Neil N Kawut Steven M SM

American journal of respiratory and critical care medicine 20090212 9

<h4>Rationale</h4>Portopulmonary hypertension (PPHTN) occurs in 6% of liver transplant candidates. The pathogenesis of this complication of portal hypertension is poorly understood.<h4>Objectives</h4>To identify genetic risk factors for PPHTN in patients with advanced liver disease.<h4>Methods</h4>We performed a multicenter case-control study of patients with portal hypertension. Cases had a mean pulmonary artery pressure >25 mm Hg, pulmonary vascular resistance >240 dynes.s(-1).cm(-5), and pulm ...[more]

PMID: 19218192

Similar Datasets

Project description:BackgroundPortopulmonary hypertension (POPH), pulmonary arterial hypertension that develops in the setting of portal hypertension, can lead to right-sided heart failure and death. Being female is a known risk factor for POPH, but little is known about the effect of sex on clinical manifestations, hemodynamics, treatment response, and survival.Research questionWe sought to characterize sex differences in clinical characteristics, pulmonary hemodynamics, treatment response, and survival in patients with POPH.Study design and methodsWe performed a retrospective cohort study of adult candidates for liver transplant (LT) who had POPH within the Organ Procurement and Transplantation Network database. Females and males were compared. Multivariate regression was performed to assess the association between sex and pulmonary vascular resistance (PVR) and survival. Patients were also stratified by age (50 years) to determine how age modifies the relationship between sex and hemodynamics and survival.ResultsWe included 190 adults (103 male, 87 female). Compared with men, women had a lower model for end-stage liver disease (MELD) score (12.1± 4.2 vs 13.8 ± 4.9; P = .01) and were more likely to have autoimmune liver disease. Women had a higher baseline PVR (610.6 ± 366.6 vs 461.0 ± 185.3 dynes-s-cm-5; P < .001) and posttreatment PVR (244.6 ± 119.5 vs 202.0 ± 87.7 dynes-s-cm-5; P = .008) and a greater treatment response (ΔPVR) (-359.3 ± 381.9 vs -260.2 ± 177.3 dynes-s-cm-5; P = .03). In multivariate analysis, female sex (or gender) remained associated with a higher baseline PVR (P = .008). Women and men had overall similar survival (P > .05). When patients were stratified by age, being female was independently associated with worse waiting list survival after adjusting for MELD and PVR in younger patients (HR, 6.61; 95% CI, 1.25-35.08; P = .03) but not in older patients.InterpretationCompared with male candidates, female candidates for LT who had POPH had a higher PVR and lower MELD score and were more likely to have autoimmune liver disease. Women and men had similar overall survival, but female sex (or gender) was associated with worse survival in younger patients.

Dataset Information

Genetic risk factors for portopulmonary hypertension in patients with advanced liver disease.

Publications

Genetic risk factors for portopulmonary hypertension in patients with advanced liver disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets