Kari E Roberts1, Michael B Fallon2, Michael J Krowka3, Raymond L Benza2, James A Knowles4, David B Badesch5, Robert S Brown6, Darren B Taichman7, James Trotter5, Steven Zacks8, Evelyn M Horn6, Steven M Kawut9. 1. Department of Medicine, Tufts Medical Center, Boston, MA. 2. Department of Medicine, University of Alabama, Birmingham, AL. 3. Department of Medicine, Mayo Clinic, Rochester, MN. 4. Department of Psychiatry, University of Southern California, Los Angeles, CA. 5. Department of Medicine, University of Colorado, Denver, CO. 6. the Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY. 7. Department of Medicine, University of Pennsylvania, Philadelphia, PA. 8. Department of Medicine, University of North Carolina, Chapel Hill, NC. 9. Department of Medicine, University of Pennsylvania, Philadelphia, PA. Electronic address: kawut@mail.med.upenn.edu.
Abstract
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.
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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