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Original Research: PULMONARY HYPERTENSION |

Serotonin Transporter Polymorphisms in Patients With Portopulmonary Hypertension

Kari E. Roberts, MD; Michael B. Fallon, MD; Michael J. Krowka, MD, FCCP; Raymond L. Benza, MD; James A. Knowles, MD, PhD; David B. Badesch, MD, FCCP; Robert S. Brown, Jr, MD; Darren B. Taichman, MD, PhD, FCCP; James Trotter, MD; Steven Zacks, MD; Evelyn M. Horn, MD; Steven M. Kawut, MD, MS, FCCP; for the Pulmonary Vascular Complications of Liver Disease Study Group
Author and Funding Information

*From the Department of Medicine (Dr. Roberts), Tufts Medical Center, Boston, MA; the Department of Medicine (Drs. Fallon and Benza), University of Alabama, Birmingham, AL; the Department of Medicine (Dr. Krowka), Mayo Clinic, Rochester, MN; the Department of Psychiatry (Dr. Knowles), University of Southern California, Los Angeles, CA; the Department of Medicine (Drs. Badesch and Trotter), University of Colorado, Denver, CO; the Department of Medicine (Drs. Brown and Horn), Columbia University College of Physicians and Surgeons, New York, NY; the Department of Medicine (Drs. Taichman and Kawut), University of Pennsylvania, Philadelphia, PA; and the Department of Medicine (Dr. Zacks), University of North Carolina, Chapel Hill, NC.

Correspondence to: Steven M. Kawut, MD, MS, FCCP, Penn Cardiovascular Institute, Center for Clinical Epidemiology and Biostatistics, Pulmonary, Allergy, and Critical Care Division, University of Pennsylvania School of Medicine, 711 Blockley Hall, 432 Guardian Dr, Philadelphia, PA 19104; e-mail: kawut@mail.med.upenn.edu

†A list of centers and members of the Pulmonary Vascular Complications of Liver Disease Study Group is located in the Appendix.


This work was supported by National Institutes of Health grants DK064103, DK065958, RR00645, RR00585, RR00046, RR00032, HL67771, and HL089812.

The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/site/misc/reprints.xhtml).


© 2009 American College of Chest Physicians


Chest. 2009;135(6):1470-1475. doi:10.1378/chest.08-1909
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Background:  The long allele of a functional promoter polymorphism in the serotonin transporter (SERT) is associated with an increased risk of some forms of pulmonary arterial hypertension. We hypothesized that the long allele or other polymorphisms in SERT would be associated with an increased risk of portopulmonary hypertension (PPHTN) in patients with advanced liver disease.

Methods:  We performed a multicenter case-control study. Subjects undergoing liver transplant evaluation at seven centers were prospectively screened for the presence of PPHTN using transthoracic echocardiography. PPHTN was confirmed by right heart catheterization using standard criteria.

Results:  The study sample included 30 case patients with PPHTN and 109 control subjects with advanced liver disease. There was no significant association between the long allele and case status in an adjusted additive model (odds ratio, 0.63; 95% confidence interval, 0.33 to 1.21; p = 0.17). If anything, LL genotype tended to be associated with a lower risk of PPHTN. There were no associations between other SERT polymorphisms and PPHTN.

Conclusions:  SERT polymorphisms are not associated with the risk of PPHTN in patients with advanced liver disease. Other clinical or genetic risk factors may play a role in this complication of portal hypertension.

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