Document Detail


Serotonin transporter polymorphisms in familial and idiopathic pulmonary arterial hypertension.
MedLine Citation:
PMID:  16339917     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
RATIONALE: Serotonin is a pulmonary vasoconstrictor and smooth muscle cell mitogen. The serotonin transporter (SERT) is abundant in pulmonary vascular smooth muscle. Compared with the short (S) allele, the long (L) SERT promoter allele is associated with increased SERT transcription and more severe pulmonary hypertension in a cohort of patients with chronic obstructive pulmonary disease, and was more prevalent in a cohort with idiopathic pulmonary arterial hypertension (IPAH), compared with control subjects.
OBJECTIVE: We hypothesized that the SERT L allele would associate with an earlier age at diagnosis and/or shorter survival interval in pulmonary arterial hypertension (PAH) than the S allele.
METHODS: SERT promoters from 166 familial PAH (FPAH), 83 IPAH, and 125 control subjects were sequenced. One hundred twenty-seven of the patients with FPAH had a known mutation in bone morphogenetic protein receptor 2 (BMPR2).
RESULTS: The mean age at diagnosis was 35.8 yr in patients with FPAH and 41.1 yr in patients with IPAH (p = 0.02). There were no significant differences in distribution of the LL, LS, or SS genotypes in IPAH, FPAH, or unaffected BMPR2 mutation carriers. In FPAH, the LL genotype was associated with an earlier age at diagnosis (p < 0.02).
CONCLUSIONS: In patients with IPAH, these SERT genotypes do not correlate with age at diagnosis or survival interval. In patients with FPAH, the LL genotype correlates with an earlier age at diagnosis than SL or SS, although survival among the groups was similar. The correlation of the SERT promoter polymorphism with age at diagnosis in FPAH suggests a possible relationship between the SERT and BMPR2.
Authors:
Elisabeth D Willers; John H Newman; James E Loyd; Ivan M Robbins; Lisa A Wheeler; Melissa A Prince; Krista C Stanton; Joy A Cogan; James R Runo; Daniel Byrne; Marc Humbert; Gerald Simonneau; Benjamin Sztrymf; Jane A Morse; James A Knowles; Kari E Roberts; Jude J McElroy; Robyn J Barst; John A Phillips
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2005-12-09
Journal Detail:
Title:  American journal of respiratory and critical care medicine     Volume:  173     ISSN:  1073-449X     ISO Abbreviation:  Am. J. Respir. Crit. Care Med.     Publication Date:  2006 Apr 
Date Detail:
Created Date:  2006-03-24     Completed Date:  2006-10-03     Revised Date:  2012-06-25    
Medline Journal Info:
Nlm Unique ID:  9421642     Medline TA:  Am J Respir Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  798-802     Citation Subset:  AIM; IM    
Affiliation:
Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Medical Center North T-1218, Nashville, TN 37232-2650, USA. elisabeth.willers@vanderbilt.edu
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MeSH Terms
Descriptor/Qualifier:
Adult
Bone Morphogenetic Protein Receptors, Type II / genetics
DNA / genetics*
Female
Genetic Predisposition to Disease
Genotype
Humans
Hypertension, Pulmonary / genetics*,  metabolism
Male
Mutation
Polymorphism, Genetic*
Prognosis
Serotonin Plasma Membrane Transport Proteins / genetics*
Grant Support
ID/Acronym/Agency:
P01 072058//PHS HHS
Chemical
Reg. No./Substance:
0/SLC6A4 protein, human; 0/Serotonin Plasma Membrane Transport Proteins; 9007-49-2/DNA; EC 2.7.11.30/BMPR2 protein, human; EC 2.7.11.30/Bone Morphogenetic Protein Receptors, Type II
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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