Serotonin transporter polymorphisms in patients with portopulmonary 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.
Roberts
Kari E
KE
Department of Medicine, Tufts Medical Center, Boston, MA.
Fallon
Michael B
MB
Department of Medicine, University of Alabama, Birmingham, AL.
Krowka
Michael J
MJ
Department of Medicine, Mayo Clinic, Rochester, MN.
Benza
Raymond L
RL
Department of Medicine, University of Alabama, Birmingham, AL.
Knowles
James A
JA
Department of Psychiatry, University of Southern California, Los Angeles, CA.
Badesch
David B
DB
Department of Medicine, University of Colorado, Denver, CO.
Brown
Robert S
RS
the Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY.
Taichman
Darren B
DB
Department of Medicine, University of Pennsylvania, Philadelphia, PA.
Trotter
James
J
Department of Medicine, University of Colorado, Denver, CO.
Zacks
Steven
S
Department of Medicine, University of North Carolina, Chapel Hill, NC.
Horn
Evelyn M
EM
the Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY.
Kawut
Steven M
SM
Department of Medicine, University of Pennsylvania, Philadelphia, PA. Electronic address: kawut@mail.med.upenn.edu.
D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D016001:Confidence Intervals; D017548:Echocardiography, Transesophageal; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D005838:Genotype; D006801:Humans; D006975:Hypertension, Portal / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D006976:Hypertension, Pulmonary / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D015994:Incidence; D008107:Liver Diseases / Q000175:diagnosis* / Q000453:epidemiology / Q000601:surgery; D016031:Liver Transplantation; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011300:Preoperative Care / Q000379:methods; D011336:Probability; D011379:Prognosis; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D012720:Severity of Illness Index; D015996:Survival Rate
D050486:Serotonin Plasma Membrane Transport Proteins