Clinical Advances in Liver, Pancrease, and Biliary TractGenetic Risk Factors for Hepatopulmonary Syndrome in Patients With Advanced Liver Disease
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Patients and Methods
For other information regarding patients and methods, please see Supplementary Patients and Methods.
Results
There were 59 cases and 126 controls included in this analysis (Table 2). The mean age of the subjects was 53 ± 10 years, 39% were female, and the majority (83%) was non-Hispanic. The majority of subjects in both groups had liver disease because of hepatitis C infection (44%) or alcohol (41%). Subjects with HPS had a mean PaO2 of 75 ± 13 mm Hg and a median alveolar-arterial oxygen gradient of 25 mm Hg (interquartile range, 19–35 mm Hg).
Of the 1086 SNPs genotyped in candidate genes, 3 assays
Discussion
Using a hypothesis-generating approach, we have identified that the possession of common genetic variation in genes associated with vascular growth and development and estrogen action and signaling was associated with HPS in this case-control study. In contrast, we did not find any association between HPS and vasoregulatory genes such as nitric oxide, heme oxygenase, and the endothelin-B receptor, which have been specifically implicated in HPS.28, 29, 30, 31 Our findings are in line with recent
Acknowledgments
The authors thank May Huang; John Schlatterer; and John O'Connor, PhD, from the Irving Institute for Clinical and Translational Research at Columbia University for their technical assistance.
References (47)
- et al.
Hepatopulmonary syndrome in patients with hypoxic hepatitis
Gastroenterology
(2006) - et al.
Impact of hepatopulmonary syndrome on quality of life and survival in liver transplant candidates
Gastroenterology
(2008) Hepatopulmonary syndrome and portopulmonary hypertension: implications for liver transplantation
Clin Chest Med
(2005)- et al.
Analysis of pulmonary heme oxygenase-1 and nitric oxide synthase alterations in experimental hepatopulmonary syndrome
Gastroenterology
(2003) - et al.
The effects of serum estrogen levels on hypoxemia and blood nitric oxide levels in experimental hepatopulmonary syndrome
Hepatol Res
(2005) - et al.
Pulmonary angiogenesis in a rat model of hepatopulmonary syndrome
Gastroenterology
(2009) - et al.
Hepatic hydrothorax: pathogenesis, diagnosis, and management
Am J Med
(1999) - et al.
PLINK: a tool set for whole-genome association and population-based linkage analyses
Am J Hum Genet
(2007) - et al.
Score tests for association between traits and haplotypes when linkage phase is ambiguous
Am J Hum Genet
(2002) - et al.
The role of endothelial nitric oxide synthase in the pathogenesis of a rat model of hepatopulmonary syndrome
Gastroenterology
(1997)
Increased pulmonary vascular endothelin B receptor expression and responsiveness to endothelin-1 in cirrhotic and portal hypertensive rats: a potential mechanism in experimental hepatopulmonary syndrome
J Hepatol
Endostatin: an endogenous inhibitor of angiogenesis and tumor growth
Cell
Hereditary hemorrhagic telangiectasia: clinical features in ENG and ALK1 mutation carriers
J Thromb Haemost
Vascular endothelial growth factor activates the Tie family of receptor tyrosine kinases
Cell Signal
Transcriptional regulation of vascular endothelial cell responses to hypoxia by HIF-1
Blood
Spermidine/spermine-N1-acetyltransferase 2 is an essential component of the ubiquitin ligase complex that regulates hypoxia-inducible factor 1α
J Biol Chem
Exhaled nitric oxide and oxygenation abnormalities in hepatic cirrhosis
Hepatology
Carboxyhemoglobin levels in cirrhotic patients with and without hepatopulmonary syndrome
Gastroenterology
Pulmonary-hepatic vascular Disorders (PHD)
Eur Respir J
Natural history of hepatopulmonary syndrome: impact of liver transplantation
Hepatology
Elevated exhaled nitric oxide in patients with hepatopulmonary syndrome
Eur Respir J
Methylene blue improves the hepatopulmonary syndrome
Ann Intern Med
Effects of nebulized N(G)-nitro-L-arginine methyl ester in patients with hepatopulmonary syndrome
Hepatology
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A listing of additional members of the Pulmonary Vascular Complications of Liver Disease Study Group can be found in Appendix 1.
Conflicts of interest The authors disclose no conflicts.