Dataset Information

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

ABSTRACT:

Rationale

Portopulmonary hypertension (PPHTN) occurs in 6% of liver transplant candidates. The pathogenesis of this complication of portal hypertension is poorly understood.

Objectives

To identify genetic risk factors for PPHTN in patients with advanced liver disease.

Methods

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.

Measurements and main results

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.

Conclusions

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

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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:Portopulmonary hypertension (POPH) is a type of pulmonary arterial hypertension occurring exclusively in those with portal hypertensive liver disease. Liver transplantation (LT) can significantly improve outcomes. Current guidelines counsel against immediate adjustments to targeted therapy after LT and suggest routine echocardiography as sufficiently informative to guide therapeutic adjustments. Current practice patterns for adjusting targeted therapy after LT in POPH, and how they compare with guidelines, are not well established. To answer this question, we performed an institutional review board-approved, cross-sectional mixed-methods survey-based study of US POPH providers. Anonymized requests to complete the survey were sent through professional networks between January 20, 2022, and April 20, 2022. Responses were compared between cardiologists and pulmonologists using Fisher's exact tests, at a significance of 0.05. A total of 85 POPH physicians were included in the final analysis (66% pulmonologists and 34% cardiologists). Following LT, the majority of respondents routinely used a combination of standard cardiopulmonary assessment modalities to guide adjustment of targeted therapy following LT. Most respondents (69%) started by adjusting parenteral prostacyclins with small titrations and frequent reassessments within 3 months of LT, but some (19.7%) adjusted targeted therapy immediately after LT. Our results showed that the majority of respondents favored serial integrated cardiopulmonary testing (including routine right heart catheterization) to guide the adjustment of targeted therapy in POPH after LT, and almost one-fifth of respondents weaned therapy immediately after LT. Our study demonstrates heterogeneity in POPH practice patterns after LT, highlights differences between current practice patterns and the most recent guidelines, emphasizes the need for additional research, and supports a team-based approach to standardize care for these high-risk patients and optimize post-LT outcomes.

Dataset Information

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

Rationale

Objectives

Methods

Measurements and main results

Conclusions

Publications

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

Similar Datasets

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