title: Serotonin transporter polymorphisms in familial and idiopathic pulmonary arterial hypertension.
abstract: BACKGROUND
  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.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
authors.forename: Elisabeth D
authors.initials: ED
authors.lastname: Willers
authors.forename: John H
authors.initials: JH
authors.lastname: Newman
authors.forename: James E
authors.initials: JE
authors.lastname: Loyd
authors.forename: Ivan M
authors.initials: IM
authors.lastname: Robbins
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Wheeler
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Prince
authors.forename: Krista C
authors.initials: KC
authors.lastname: Stanton
authors.forename: Joy A
authors.initials: JA
authors.lastname: Cogan
authors.forename: James R
authors.initials: JR
authors.lastname: Runo
authors.forename: Daniel
authors.initials: D
authors.lastname: Byrne
authors.forename: Marc
authors.initials: M
authors.lastname: Humbert
authors.forename: Gerald
authors.initials: G
authors.lastname: Simonneau
authors.forename: Benjamin
authors.initials: B
authors.lastname: Sztrymf
authors.forename: Jane A
authors.initials: JA
authors.lastname: Morse
authors.forename: James A
authors.initials: JA
authors.lastname: Knowles
authors.forename: Kari E
authors.initials: KE
authors.lastname: Roberts
authors.forename: Jude J
authors.initials: JJ
authors.lastname: McElroy
authors.forename: Robyn J
authors.initials: RJ
authors.lastname: Barst
authors.forename: John A
authors.initials: JA
authors.lastname: Phillips
mesh_terms: D000328:Adult; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000235:genetics; D004247:DNA / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006976:Hypertension, Pulmonary / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009154:Mutation; D011110:Polymorphism, Genetic; D011379:Prognosis; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D004247:DNA; C498218:BMPR2 protein, human; D052006:Bone Morphogenetic Protein Receptors, Type II